Skip to main content
Top
Published in: Acta Diabetologica 4/2014

01-08-2014 | Original Article

Common polymorphisms in MIR146a, MIR128a and MIR27a genes contribute to neuropathy susceptibility in type 2 diabetes

Authors: Cinzia Ciccacci, Roberto Morganti, Davide Di Fusco, Cinzia D’Amato, Laura Cacciotti, Carla Greco, Sara Rufini, Giuseppe Novelli, Federica Sangiuolo, Girolama A. Marfia, Paola Borgiani, Vincenza Spallone

Published in: Acta Diabetologica | Issue 4/2014

Login to get access

Abstract

Diabetic polyneuropathy (DPN) and cardiovascular autonomic neuropathy (CAN) are common type 2 diabetes complications with a large inter-individual variability in terms of clinical manifestations and severity. Our aim was to evaluate a possible involvement of genetic polymorphisms in miRNA regions in the susceptibility to DPN and CAN. Nine polymorphisms in miRNA genes were studied in a sample of 132 type 2 diabetes patients (T2D) analysed for DPN and 128 T2D patients analysed for CAN. A genotype–phenotype correlation analysis was performed. The T allele of rs11888095 single nucleotide polymorphism (SNP) in MIR128a was significantly associated with a higher risk (ORadj = 4.89, P adj = 0.02), whereas the C allele of rs2910164 SNP in MIR146a was associated with a lower risk to develop DPN (ORadj = 0.49, P adj = 0.09), respectively. A multivariate logistic regression analysis confirmed that both SNPs contribute to DPN (p < 0.001 and p = 0.01 for MIR128a and MIR146a, respectively). MIR128a SNP significantly contributed also to DPN score (p = 0.026). Rs895819 SNP in MIR27a was significantly associated with a higher risk to develop early CAN (P adj = 0.023 and ORadj = 3.43). The rs2910164 SNP in MIR146a showed a protective effect respect to early CAN (P adj = 0.052, ORadj = 0.32) and to confirmed CAN (P adj = 0.041, ORadj = 0.13). The same SNP resulted significantly associated with a lower CAN score and a higher E/I (p = 0.002 and p = 0.003, respectively). In conclusion, we described associations of MIR128a and MIR146a SNPs with DPN susceptibility and of MIR146a and MIR27a SNPs with CAN susceptibility. This is the first study showing that genetic variability in miRNA genes could be involved in diabetic neuropathies susceptibility.
Appendix
Available only for authorised users
Literature
1.
go back to reference Dyck PJ, Albers JW, Andersen H, Arezzo JC, Biessels GJ, Bril V, Feldman EL, Litchy WJ, O’Brien PC, Russell JW; on behalf of the Toronto Expert Panel on Diabetic Neuropathy* (2011) Diabetic polyneuropathies: update on research definition, diagnostic criteria and estimation of severity. Diabetes Metab Res Rev doi: 10.1002/dmrr.1226 Dyck PJ, Albers JW, Andersen H, Arezzo JC, Biessels GJ, Bril V, Feldman EL, Litchy WJ, O’Brien PC, Russell JW; on behalf of the Toronto Expert Panel on Diabetic Neuropathy* (2011) Diabetic polyneuropathies: update on research definition, diagnostic criteria and estimation of severity. Diabetes Metab Res Rev doi: 10.​1002/​dmrr.​1226
2.
go back to reference Yagihashi S, Mizukami H, Sugimoto K (2011) Mechanism of diabetic neuropathy: where are we now and where to go? J Diabetes Invest 2(1):18–32CrossRef Yagihashi S, Mizukami H, Sugimoto K (2011) Mechanism of diabetic neuropathy: where are we now and where to go? J Diabetes Invest 2(1):18–32CrossRef
3.
go back to reference Fedele D, Comi G, Coscelli C, Cucinotta D, Feldman EL, Ghirlanda G, Greene DA, Negrin P, Santeusanio F (1997) A multicenter study on the prevalence of diabetic neuropathy in Italy. Italian diabetic neuropathy committee. Diabetes Care 20(5):836–843PubMedCrossRef Fedele D, Comi G, Coscelli C, Cucinotta D, Feldman EL, Ghirlanda G, Greene DA, Negrin P, Santeusanio F (1997) A multicenter study on the prevalence of diabetic neuropathy in Italy. Italian diabetic neuropathy committee. Diabetes Care 20(5):836–843PubMedCrossRef
4.
go back to reference Várkonyi T, Kempler P (2008) Diabetic neuropathy: new strategies for treatment. Diabetes Obes Metab 10:99–108PubMed Várkonyi T, Kempler P (2008) Diabetic neuropathy: new strategies for treatment. Diabetes Obes Metab 10:99–108PubMed
5.
go back to reference Tesfaye S, Boulton AJ, Dyck PJ, Freeman R, Horowitz M, Kempler P, Lauria G, Malik RA, Spallone V, Vinik A, Bernardi L, Valensi P; Toronto Diabetic Neuropathy Expert Group (2010) Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care 33(10):2285–2293CrossRef Tesfaye S, Boulton AJ, Dyck PJ, Freeman R, Horowitz M, Kempler P, Lauria G, Malik RA, Spallone V, Vinik A, Bernardi L, Valensi P; Toronto Diabetic Neuropathy Expert Group (2010) Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care 33(10):2285–2293CrossRef
6.
go back to reference Gries FA, Cameron NE, Low PA, Ziegler D (2003) Textbook of diabetic neuropathy. Thieme, Stuttgard, pp 64–82 Gries FA, Cameron NE, Low PA, Ziegler D (2003) Textbook of diabetic neuropathy. Thieme, Stuttgard, pp 64–82
7.
go back to reference Papanas N, Vinik AI, Ziegler D (2011) Neuropathy in prediabetes: does the clock start ticking early? Nat Rev Endocrinol 7:682–690PubMed Papanas N, Vinik AI, Ziegler D (2011) Neuropathy in prediabetes: does the clock start ticking early? Nat Rev Endocrinol 7:682–690PubMed
8.
go back to reference Spallone V, Bellavere F, Scionti L, Maule S, Quadri R, Bax G, Melga P, Viviani GL, Esposito K, Morganti R, Cortelli P; Diabetic Neuropathy Study Group of the Italian Society of Diabetology (2011) Recommendations for the use of cardiovascular tests in diagnosing diabetic autonomic neuropathy. Nutr Metab Cardiovasc Dis 21(1):69–78CrossRef Spallone V, Bellavere F, Scionti L, Maule S, Quadri R, Bax G, Melga P, Viviani GL, Esposito K, Morganti R, Cortelli P; Diabetic Neuropathy Study Group of the Italian Society of Diabetology (2011) Recommendations for the use of cardiovascular tests in diagnosing diabetic autonomic neuropathy. Nutr Metab Cardiovasc Dis 21(1):69–78CrossRef
9.
go back to reference Töyry JP, Partanen JV, Niskanen LK, Länsimies EA, Uusitupa MI (1997) Divergent development of autonomic and peripheral somatic neuropathies in NIDDM. Diabetologia 40(8):953–958PubMedCrossRef Töyry JP, Partanen JV, Niskanen LK, Länsimies EA, Uusitupa MI (1997) Divergent development of autonomic and peripheral somatic neuropathies in NIDDM. Diabetologia 40(8):953–958PubMedCrossRef
10.
go back to reference Gaede P, Pedersen O (2004) Intensive integrated therapy of type 2 diabetes: implications for long-term prognosis. Diabetes 53(Suppl 3):S39–S47PubMedCrossRef Gaede P, Pedersen O (2004) Intensive integrated therapy of type 2 diabetes: implications for long-term prognosis. Diabetes 53(Suppl 3):S39–S47PubMedCrossRef
11.
go back to reference Jurado J, Ybarra J, Romeo JH, Garcia M, Zabaleta-Del-Olmo E (2012) Angiotensin-converting enzyme gene single polymorphism as a genetic biomarker of diabetic peripheral neuropathy: longitudinal prospective study. J Diabetes Complicat 26(2):77–82PubMedCrossRef Jurado J, Ybarra J, Romeo JH, Garcia M, Zabaleta-Del-Olmo E (2012) Angiotensin-converting enzyme gene single polymorphism as a genetic biomarker of diabetic peripheral neuropathy: longitudinal prospective study. J Diabetes Complicat 26(2):77–82PubMedCrossRef
12.
go back to reference Mansoor Q, Javaid A, Bilal N, Ismail M (2012) Angiotensin-converting enzyme (ACE) gene II genotype protects against the development of diabetic peripheral neuropathy in type 2 diabetes mellitus. J Diabetes 4(3):257–261PubMedCrossRef Mansoor Q, Javaid A, Bilal N, Ismail M (2012) Angiotensin-converting enzyme (ACE) gene II genotype protects against the development of diabetic peripheral neuropathy in type 2 diabetes mellitus. J Diabetes 4(3):257–261PubMedCrossRef
13.
go back to reference Yigit S, Karakus N, Inanir A (2013) Association of MTHFR gene C677T mutation with diabetic peripheral neuropathy and diabetic retinopathy. Mol Vis 19:1626–1630PubMedCentralPubMed Yigit S, Karakus N, Inanir A (2013) Association of MTHFR gene C677T mutation with diabetic peripheral neuropathy and diabetic retinopathy. Mol Vis 19:1626–1630PubMedCentralPubMed
14.
go back to reference Vojtková J, Ďurdík P, Čiljaková M, Michnová Z, Turčan T, Babušíková E (2013) The association between glutathione S-transferase T1 and M1 gene polymorphisms and cardiovascular autonomic neuropathy in Slovak adolescents with type 1 diabetes mellitus. J Diabetes Complicat 27(1):44–48PubMedCrossRef Vojtková J, Ďurdík P, Čiljaková M, Michnová Z, Turčan T, Babušíková E (2013) The association between glutathione S-transferase T1 and M1 gene polymorphisms and cardiovascular autonomic neuropathy in Slovak adolescents with type 1 diabetes mellitus. J Diabetes Complicat 27(1):44–48PubMedCrossRef
15.
go back to reference Karolina DS, Armugam A, Sepramaniam S (2012) MiRNAs and diabetes mellitus. Expert Rev Endocrinol Metab 7(3):281–300CrossRef Karolina DS, Armugam A, Sepramaniam S (2012) MiRNAs and diabetes mellitus. Expert Rev Endocrinol Metab 7(3):281–300CrossRef
16.
17.
go back to reference Sun G, Yan J, Noltner K, Feng J, Li H, Sarkis DA, Sommer SS, Rossi JJ (2009) SNPs in human miRNA genes affect biogenesis and function. RNA 15(9):1640–1651PubMedCentralPubMedCrossRef Sun G, Yan J, Noltner K, Feng J, Li H, Sarkis DA, Sommer SS, Rossi JJ (2009) SNPs in human miRNA genes affect biogenesis and function. RNA 15(9):1640–1651PubMedCentralPubMedCrossRef
18.
go back to reference Ciccacci C, Di Fusco D, Cacciotti L, Morganti R, D’Amato C, Greco C, Rufini S, Novelli G, Sangiuolo F, Spallone V, Borgiani P (2013) MicroRNA genetic variations: association with type 2 diabetes. Acta Diabetol 50(6):867–872PubMedCrossRef Ciccacci C, Di Fusco D, Cacciotti L, Morganti R, D’Amato C, Greco C, Rufini S, Novelli G, Sangiuolo F, Spallone V, Borgiani P (2013) MicroRNA genetic variations: association with type 2 diabetes. Acta Diabetol 50(6):867–872PubMedCrossRef
19.
go back to reference Bril V, Perkins BA (2002) Validation of the Toronto clinical scoring system for diabetic polyneuropathy. Diabetes Care 25(11):2048–2052PubMedCrossRef Bril V, Perkins BA (2002) Validation of the Toronto clinical scoring system for diabetic polyneuropathy. Diabetes Care 25(11):2048–2052PubMedCrossRef
20.
go back to reference Bax G, Fagherazzi C, Piarulli F, Nicolucci A, Fedele D (1996) Reproducibility of Michigan neuropathy screening instrument (MNSI): a comparison with tests using the vibratory and thermal perception thresholds. Diabetes Care 19(8):904–905PubMed Bax G, Fagherazzi C, Piarulli F, Nicolucci A, Fedele D (1996) Reproducibility of Michigan neuropathy screening instrument (MNSI): a comparison with tests using the vibratory and thermal perception thresholds. Diabetes Care 19(8):904–905PubMed
21.
go back to reference Zinman LH, Bril V, Perkins BA (2004) Cooling detection thresholds in the assessment of diabetic sensory polyneuropathy: comparison of CASE IV and Medoc instruments. Diabetes Care 27(7):1674–1679PubMedCrossRef Zinman LH, Bril V, Perkins BA (2004) Cooling detection thresholds in the assessment of diabetic sensory polyneuropathy: comparison of CASE IV and Medoc instruments. Diabetes Care 27(7):1674–1679PubMedCrossRef
22.
go back to reference Bouhassira D, Attal N, Alchaar H, Boureau F, Brochet B, Bruxelle J, Cunin G, Fermanian J, Ginies P, Grun-Overdyking A, Jafari-Schluep H, Lantéri-Minet M, Laurent B, Mick G, Serrie A, Valade D, Vicaut E (2005) Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain 114:29–36PubMedCrossRef Bouhassira D, Attal N, Alchaar H, Boureau F, Brochet B, Bruxelle J, Cunin G, Fermanian J, Ginies P, Grun-Overdyking A, Jafari-Schluep H, Lantéri-Minet M, Laurent B, Mick G, Serrie A, Valade D, Vicaut E (2005) Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain 114:29–36PubMedCrossRef
23.
go back to reference Spallone V, Morganti R, D’Amato C, Greco C, Cacciotti L, Marfia GA (2012) Validation of DN4 as a screening tool for neuropathic pain in painful diabetic polyneuropathy. Diabet Med 29:578–585PubMedCrossRef Spallone V, Morganti R, D’Amato C, Greco C, Cacciotti L, Marfia GA (2012) Validation of DN4 as a screening tool for neuropathic pain in painful diabetic polyneuropathy. Diabet Med 29:578–585PubMedCrossRef
24.
go back to reference Stålberg E, Falck B, Gilai A, Jabre J, Sonoo M, Todnem K (1999) Standards for quantification of EMG and neurography. The international federation of clinical neurophysiology. Electroencephalogr Clin Neurophysiol Suppl 52:213–220PubMed Stålberg E, Falck B, Gilai A, Jabre J, Sonoo M, Todnem K (1999) Standards for quantification of EMG and neurography. The international federation of clinical neurophysiology. Electroencephalogr Clin Neurophysiol Suppl 52:213–220PubMed
25.
go back to reference Dunnigan SK, Ebadi H, Breiner A, Katzberg HD, Lovblom LE, Perkins BA, Bril V (2013) Conduction slowing in diabetic sensorimotor polyneuropathy. Diabetes Care 36:3684–3690PubMedCrossRef Dunnigan SK, Ebadi H, Breiner A, Katzberg HD, Lovblom LE, Perkins BA, Bril V (2013) Conduction slowing in diabetic sensorimotor polyneuropathy. Diabetes Care 36:3684–3690PubMedCrossRef
27.
go back to reference Lorenzen J, Kumarswamy R, Dangwal S, Thum T (2012) MicroRNAs in diabetes and diabetes-associated complications. RNA Biol 9(6):820–827PubMedCrossRef Lorenzen J, Kumarswamy R, Dangwal S, Thum T (2012) MicroRNAs in diabetes and diabetes-associated complications. RNA Biol 9(6):820–827PubMedCrossRef
28.
go back to reference Kovacs B, Lumayag S, Cowan C, Xu S (2011) MicroRNAs in early diabetic retinopathy in streptozotocin-induced diabetic rats. Invest Ophthalmol Vis Sci 52(7):4402–4409PubMedCrossRef Kovacs B, Lumayag S, Cowan C, Xu S (2011) MicroRNAs in early diabetic retinopathy in streptozotocin-induced diabetic rats. Invest Ophthalmol Vis Sci 52(7):4402–4409PubMedCrossRef
29.
go back to reference Feng B, Chen S, McArthur K, Wu Y, Sen S, Ding Q, Feldman RD, Chakrabarti S (2011) miR-146a-mediated extracellular matrix protein production in chronic diabetes complications. Diabetes 60(11):2975–2984PubMedCentralPubMedCrossRef Feng B, Chen S, McArthur K, Wu Y, Sen S, Ding Q, Feldman RD, Chakrabarti S (2011) miR-146a-mediated extracellular matrix protein production in chronic diabetes complications. Diabetes 60(11):2975–2984PubMedCentralPubMedCrossRef
30.
go back to reference McArthur K, Feng B, Wu Y, Chen S, Chakrabarti S (2011) MicroRNA-200b regulates vascular endothelial growth factor-mediated alterations in diabetic retinopathy. Diabetes 60(4):1314–1323PubMedCentralPubMedCrossRef McArthur K, Feng B, Wu Y, Chen S, Chakrabarti S (2011) MicroRNA-200b regulates vascular endothelial growth factor-mediated alterations in diabetic retinopathy. Diabetes 60(4):1314–1323PubMedCentralPubMedCrossRef
31.
go back to reference Silva VA, Polesskaya A, Sousa TA, Corrêa VM, André ND, Reis RI, Kettelhut IC, Harel-Bellan A, De Lucca FL (2011) Expression and cellular localization of microRNA-29b and RAX, an activator of the RNA-dependent protein kinase (PKR), in the retina of streptozotocin-induced diabetic rats. Mol Vis 17:2228–2240PubMedCentralPubMed Silva VA, Polesskaya A, Sousa TA, Corrêa VM, André ND, Reis RI, Kettelhut IC, Harel-Bellan A, De Lucca FL (2011) Expression and cellular localization of microRNA-29b and RAX, an activator of the RNA-dependent protein kinase (PKR), in the retina of streptozotocin-induced diabetic rats. Mol Vis 17:2228–2240PubMedCentralPubMed
32.
go back to reference Du B, Ma LM, Huang MB, Zhou H, Huang HL, Shao P, Chen YQ, Qu LH (2010) High glucose down-regulates miR-29a to increase collagen IV production in HK-2 cells. FEBS Lett 584(4):811–816PubMedCrossRef Du B, Ma LM, Huang MB, Zhou H, Huang HL, Shao P, Chen YQ, Qu LH (2010) High glucose down-regulates miR-29a to increase collagen IV production in HK-2 cells. FEBS Lett 584(4):811–816PubMedCrossRef
33.
go back to reference Srivastava K, Srivastava A (2012) Comprehensive review of genetic association studies and meta-analyses on miRNA polymorphisms and cancer risk. PLoS One 7(11):e50966PubMedCentralPubMedCrossRef Srivastava K, Srivastava A (2012) Comprehensive review of genetic association studies and meta-analyses on miRNA polymorphisms and cancer risk. PLoS One 7(11):e50966PubMedCentralPubMedCrossRef
34.
go back to reference Wang PY, Gao ZH, Jiang ZH, Li XX, Jiang BF, Xie SY (2013) The associations of single nucleotide polymorphisms in miR-146a, miR-196a and miR-499 with breast cancer susceptibility. PLoS One 8(9):e70656PubMedCentralPubMedCrossRef Wang PY, Gao ZH, Jiang ZH, Li XX, Jiang BF, Xie SY (2013) The associations of single nucleotide polymorphisms in miR-146a, miR-196a and miR-499 with breast cancer susceptibility. PLoS One 8(9):e70656PubMedCentralPubMedCrossRef
35.
go back to reference Chen HF, Hu TT, Zheng XY, Li MQ, Luo MH, Yao YX, Chen Q, Yu SY (2013) Association between miR-146a rs2910164 polymorphism and autoimmune diseases susceptibility: a meta-analysis. Gene 521(2):259–264PubMedCrossRef Chen HF, Hu TT, Zheng XY, Li MQ, Luo MH, Yao YX, Chen Q, Yu SY (2013) Association between miR-146a rs2910164 polymorphism and autoimmune diseases susceptibility: a meta-analysis. Gene 521(2):259–264PubMedCrossRef
36.
go back to reference Luo X, Yang W, Ye DQ, Cui H, Zhang Y, Hirankarn N, Qian X, Tang Y, Lau YL, de Vries N, Tak PP, Tsao BP, Shen N (2011) A functional variant in microRNA-146a promoter modulates its expression and confers disease risk for systemic lupus erythematosus. PLoS Genet 7(6):e1002128PubMedCentralPubMedCrossRef Luo X, Yang W, Ye DQ, Cui H, Zhang Y, Hirankarn N, Qian X, Tang Y, Lau YL, de Vries N, Tak PP, Tsao BP, Shen N (2011) A functional variant in microRNA-146a promoter modulates its expression and confers disease risk for systemic lupus erythematosus. PLoS Genet 7(6):e1002128PubMedCentralPubMedCrossRef
37.
go back to reference Yang B, Zhang JL, Shi YY, Li DD, Chen J, Huang ZC, Cai B, Song XB, Li LX, Ying BW, Wang LL (2011) Association study of single nucleotide polymorphisms in pre-miRNA and rheumatoid arthritis in a Han Chinese population. Mol Biol Rep 38(8):4913–4919PubMedCrossRef Yang B, Zhang JL, Shi YY, Li DD, Chen J, Huang ZC, Cai B, Song XB, Li LX, Ying BW, Wang LL (2011) Association study of single nucleotide polymorphisms in pre-miRNA and rheumatoid arthritis in a Han Chinese population. Mol Biol Rep 38(8):4913–4919PubMedCrossRef
38.
go back to reference Green MJ, Cairns MJ, Wu J, Dragovic M, Jablensky A, Tooney PA, Scott RJ, Carr VJ, Australian Schizophrenia Research Bank (2013) Genome-wide supported variant MIR137 and severe negative symptoms predict membership of an impaired cognitive subtype of schizophrenia. Mol Psychiatry 18(7):774–780PubMedCrossRef Green MJ, Cairns MJ, Wu J, Dragovic M, Jablensky A, Tooney PA, Scott RJ, Carr VJ, Australian Schizophrenia Research Bank (2013) Genome-wide supported variant MIR137 and severe negative symptoms predict membership of an impaired cognitive subtype of schizophrenia. Mol Psychiatry 18(7):774–780PubMedCrossRef
39.
go back to reference Tang Y, Luo X, Cui H, Ni X, Yuan M, Guo Y, Huang X, Zhou H, de Vries N, Tak PP, Chen S, Shen N (2009) MicroRNA-146A contributes to abnormal activation of the type I interferon pathway in human lupus by targeting the key signaling proteins. Arthr Rheum 60:1065–1075CrossRef Tang Y, Luo X, Cui H, Ni X, Yuan M, Guo Y, Huang X, Zhou H, de Vries N, Tak PP, Chen S, Shen N (2009) MicroRNA-146A contributes to abnormal activation of the type I interferon pathway in human lupus by targeting the key signaling proteins. Arthr Rheum 60:1065–1075CrossRef
40.
go back to reference Li D, Wang T, Song X, Qucuo M, Yang B, Zhang J, Wang J, Ying B, Tao C, Wang L (2011) Genetic study of two single nucleotide polymorphisms within corresponding microRNAs and susceptibility to tuberculosis in a Chinese Tibetan and Han population. Hum Immunol 72(7):598–602PubMedCrossRef Li D, Wang T, Song X, Qucuo M, Yang B, Zhang J, Wang J, Ying B, Tao C, Wang L (2011) Genetic study of two single nucleotide polymorphisms within corresponding microRNAs and susceptibility to tuberculosis in a Chinese Tibetan and Han population. Hum Immunol 72(7):598–602PubMedCrossRef
41.
go back to reference Jazdzewski K, Liyanarachchi S, Swierniak M, Pachucki J, Ringel MD, Jarzab B, de la Chapelle A (2009) Polymorphic mature microRNAs from passenger strand of pre-miR-146a contribute to thyroid cancer. Proc Natl Acad Sci USA 106(5):1502–1505PubMedCentralPubMedCrossRef Jazdzewski K, Liyanarachchi S, Swierniak M, Pachucki J, Ringel MD, Jarzab B, de la Chapelle A (2009) Polymorphic mature microRNAs from passenger strand of pre-miR-146a contribute to thyroid cancer. Proc Natl Acad Sci USA 106(5):1502–1505PubMedCentralPubMedCrossRef
42.
go back to reference Balasubramanyam M, Aravind S, Gokulakrishnan K, Prabu P, Sathishkumar C, Ranjani H, Mohan V (2011) Impaired miR-146a expression links subclinical inflammation and insulin resistance in Type 2 diabetes. Mol Cell Biochem 351(1–2):197–205PubMedCrossRef Balasubramanyam M, Aravind S, Gokulakrishnan K, Prabu P, Sathishkumar C, Ranjani H, Mohan V (2011) Impaired miR-146a expression links subclinical inflammation and insulin resistance in Type 2 diabetes. Mol Cell Biochem 351(1–2):197–205PubMedCrossRef
43.
go back to reference Hou J, Wang P, Lin L, Liu X, Ma F, An H, Wang Z, Cao X (2009) MicroRNA-146a feedback inhibits RIG-I-dependent type I IFN production in macrophages by targeting TRAF6, IRAK1, and IRAK2. J Immunol 183:2150–2158PubMedCrossRef Hou J, Wang P, Lin L, Liu X, Ma F, An H, Wang Z, Cao X (2009) MicroRNA-146a feedback inhibits RIG-I-dependent type I IFN production in macrophages by targeting TRAF6, IRAK1, and IRAK2. J Immunol 183:2150–2158PubMedCrossRef
44.
go back to reference Bhaumik D, Scott GK, Schokrpur S, Patil CK, Campisi J, Benz CC (2008) Expression of microRNA-146 suppresses NF-kappaB activity with reduction of metastatic potential in breast cancer cells. Oncogene 27(42):5643–5647PubMedCentralPubMedCrossRef Bhaumik D, Scott GK, Schokrpur S, Patil CK, Campisi J, Benz CC (2008) Expression of microRNA-146 suppresses NF-kappaB activity with reduction of metastatic potential in breast cancer cells. Oncogene 27(42):5643–5647PubMedCentralPubMedCrossRef
45.
go back to reference Pauley KM, Satoh M, Chan AL, Bubb MR, Reeves WH, Chan EK (2008) Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients. Arthr Res Ther 10:R101CrossRef Pauley KM, Satoh M, Chan AL, Bubb MR, Reeves WH, Chan EK (2008) Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients. Arthr Res Ther 10:R101CrossRef
46.
go back to reference Ramkaran P, Khan S, Phulukdaree A, Moodley D, Chuturgoon AA (2013) miR-146a polymorphism influences levels of miR-146a, IRAK-1, and TRAF-6 in young patients with coronary artery disease. Cell Biochem Biophys. doi:10.1007/s12013-013-9704-7 Ramkaran P, Khan S, Phulukdaree A, Moodley D, Chuturgoon AA (2013) miR-146a polymorphism influences levels of miR-146a, IRAK-1, and TRAF-6 in young patients with coronary artery disease. Cell Biochem Biophys. doi:10.​1007/​s12013-013-9704-7
47.
go back to reference Cameron NE, Cotter MA (2008) Pro-inflammatory mechanisms in diabetic neuropathy: focus on the nuclear factor kappa B pathway. Curr Drug Target 9(1):60–67CrossRef Cameron NE, Cotter MA (2008) Pro-inflammatory mechanisms in diabetic neuropathy: focus on the nuclear factor kappa B pathway. Curr Drug Target 9(1):60–67CrossRef
48.
go back to reference Obrosova IG (2009) Diabetic painful and insensate neuropathy: pathogenesis and potential treatments. Neurotherapeutics 6(4):638–647PubMedCrossRef Obrosova IG (2009) Diabetic painful and insensate neuropathy: pathogenesis and potential treatments. Neurotherapeutics 6(4):638–647PubMedCrossRef
49.
go back to reference Herder C, Lankisch M, Ziegler D, Rathmann W, Koenig W, Illig T, Döring A, Thorand B, Holle R, Giani G, Martin S, Meisinger C (2009) Subclinical inflammation and diabetic polyneuropathy: MONICA/KORA survey F3 (Augsburg, Germany). Diabetes Care 32(4):680–682PubMedCentralPubMedCrossRef Herder C, Lankisch M, Ziegler D, Rathmann W, Koenig W, Illig T, Döring A, Thorand B, Holle R, Giani G, Martin S, Meisinger C (2009) Subclinical inflammation and diabetic polyneuropathy: MONICA/KORA survey F3 (Augsburg, Germany). Diabetes Care 32(4):680–682PubMedCentralPubMedCrossRef
50.
go back to reference Doupis J, Lyons TE, Wu S, Gnardellis C, Dinh T, Veves A (2009) Microvascular reactivity and inflammatory cytokines in painful and painless peripheral diabetic neuropathy. J Clin Endocrinol Metab 94(6):2157–2163PubMedCentralPubMedCrossRef Doupis J, Lyons TE, Wu S, Gnardellis C, Dinh T, Veves A (2009) Microvascular reactivity and inflammatory cytokines in painful and painless peripheral diabetic neuropathy. J Clin Endocrinol Metab 94(6):2157–2163PubMedCentralPubMedCrossRef
51.
go back to reference Spallone V, Greco C (2013) Painful and painless diabetic neuropathy: one disease or two? Curr Diabetes Rep 13(4):533–549CrossRef Spallone V, Greco C (2013) Painful and painless diabetic neuropathy: one disease or two? Curr Diabetes Rep 13(4):533–549CrossRef
52.
go back to reference Sajadieh A, Nielsen OW, Rasmussen V, Hein HO, Abedini S, Hansen JF (2004) Increased heart rate and reduced heart-rate variability are associated with subclinical inflammation in middle-aged and elderly subjects with no apparent heart disease. Eur Heart J 25(5):363–370PubMedCrossRef Sajadieh A, Nielsen OW, Rasmussen V, Hein HO, Abedini S, Hansen JF (2004) Increased heart rate and reduced heart-rate variability are associated with subclinical inflammation in middle-aged and elderly subjects with no apparent heart disease. Eur Heart J 25(5):363–370PubMedCrossRef
53.
go back to reference Sloan RP, McCreath H, Tracey KJ, Sidney S, Liu K, Seeman T (2007) RR interval variability is inversely related to inflammatory markers: the CARDIA study. Mol Med 13(3–4):178–184PubMedCentralPubMed Sloan RP, McCreath H, Tracey KJ, Sidney S, Liu K, Seeman T (2007) RR interval variability is inversely related to inflammatory markers: the CARDIA study. Mol Med 13(3–4):178–184PubMedCentralPubMed
54.
go back to reference Lanza GA, Pitocco D, Navarese EP, Sestito A, Sgueglia GA, Manto A, Infusino F, Musella T, Ghirlanda G, Crea F (2007) Association between cardiac autonomic dysfunction and inflammation in type 1 diabetic patients: effect of beta-blockade. Eur Heart J 28(7):814–820PubMedCrossRef Lanza GA, Pitocco D, Navarese EP, Sestito A, Sgueglia GA, Manto A, Infusino F, Musella T, Ghirlanda G, Crea F (2007) Association between cardiac autonomic dysfunction and inflammation in type 1 diabetic patients: effect of beta-blockade. Eur Heart J 28(7):814–820PubMedCrossRef
55.
go back to reference Lieb DC, Parson HK, Mamikunian G, Vinik AI (2012) Cardiac autonomic imbalance in newly diagnosed and established diabetes is associated with markers of adipose tissue inflammation. Exp Diabetes Res 2012:878760PubMedCentralPubMedCrossRef Lieb DC, Parson HK, Mamikunian G, Vinik AI (2012) Cardiac autonomic imbalance in newly diagnosed and established diabetes is associated with markers of adipose tissue inflammation. Exp Diabetes Res 2012:878760PubMedCentralPubMedCrossRef
56.
go back to reference Grant RW, Moore AF, Florez JC (2009) Genetic architecture of type 2 diabetes: recent progress and clinical implications. Diabetes Care 32(6):1107–1114PubMedCentralPubMedCrossRef Grant RW, Moore AF, Florez JC (2009) Genetic architecture of type 2 diabetes: recent progress and clinical implications. Diabetes Care 32(6):1107–1114PubMedCentralPubMedCrossRef
57.
go back to reference Motohashi N, Alexander MS, Shimizu-Motohashi Y, Myers JA, Kawahara G, Kunkel LM (2013) Regulation of IRS1/Akt insulin signaling by microRNA-128a during myogenesis. J Cell Sci 126(Pt 12):2678–2691PubMedCentralPubMedCrossRef Motohashi N, Alexander MS, Shimizu-Motohashi Y, Myers JA, Kawahara G, Kunkel LM (2013) Regulation of IRS1/Akt insulin signaling by microRNA-128a during myogenesis. J Cell Sci 126(Pt 12):2678–2691PubMedCentralPubMedCrossRef
58.
go back to reference Guerau-de-Arellano M, Smith KM, Godlewski J, Liu Y, Winger R, Lawler SE, Whitacre CC, Racke MK, Lovett-Racke AE (2011) Micro-RNA dysregulation in multiple sclerosis favours pro-inflammatory T-cell-mediated autoimmunity. Brain 134(Pt 12):3578–3589PubMedCrossRef Guerau-de-Arellano M, Smith KM, Godlewski J, Liu Y, Winger R, Lawler SE, Whitacre CC, Racke MK, Lovett-Racke AE (2011) Micro-RNA dysregulation in multiple sclerosis favours pro-inflammatory T-cell-mediated autoimmunity. Brain 134(Pt 12):3578–3589PubMedCrossRef
59.
go back to reference Narasimhan M, Patel D, Vedpathak D, Rathinam M, Henderson G, Mahimainathan L (2012) Identification of novel microRNAs in post-transcriptional control of Nrf2 expression and redox homeostasis in neuronal, SH-SY5Y cells. PLoS One 7(12):e51111PubMedCentralPubMedCrossRef Narasimhan M, Patel D, Vedpathak D, Rathinam M, Henderson G, Mahimainathan L (2012) Identification of novel microRNAs in post-transcriptional control of Nrf2 expression and redox homeostasis in neuronal, SH-SY5Y cells. PLoS One 7(12):e51111PubMedCentralPubMedCrossRef
Metadata
Title
Common polymorphisms in MIR146a, MIR128a and MIR27a genes contribute to neuropathy susceptibility in type 2 diabetes
Authors
Cinzia Ciccacci
Roberto Morganti
Davide Di Fusco
Cinzia D’Amato
Laura Cacciotti
Carla Greco
Sara Rufini
Giuseppe Novelli
Federica Sangiuolo
Girolama A. Marfia
Paola Borgiani
Vincenza Spallone
Publication date
01-08-2014
Publisher
Springer Milan
Published in
Acta Diabetologica / Issue 4/2014
Print ISSN: 0940-5429
Electronic ISSN: 1432-5233
DOI
https://doi.org/10.1007/s00592-014-0582-2

Other articles of this Issue 4/2014

Acta Diabetologica 4/2014 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.