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Published in: BMC Medical Genetics 1/2013

Open Access 01-12-2013 | Research article

The 3′-UTR of the adiponectin Q gene harbours susceptibility loci for atherosclerosis and its metabolic risk traits

Authors: Nzioka Muiya, Mohammed Al-Najai, Asma I Tahir, Samar Elhawari, Daisy Gueco, Editha Andres, Nejat Mazhar, Nada Altassan, Brian F Meyer, Maie Alshahid, Nduna Dzimiri

Published in: BMC Medical Genetics | Issue 1/2013

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Abstract

Background

Adiponectin Q is a hormone that modulates several metabolic processes and contributes to the suppression of biochemical pathways leading to metabolic syndrome. Hence, polymorphic changes in the adiponectin Q (ADIPOQ) gene are likely to contribute to metabolic disorders, and consequently lead to atherosclerosis. In the present study, we performed a population-based association study for 8 SNPs in 4646 Saudi individuals (2339 CAD cases versus angiographed 2307 controls) by real-time PCR.

Methods

Linkage analysis was done by the Affymetrix Gene Chip array, sequencing by the MegaBACE DNA analysis system and genotyping accomplished by TaqMan chemistry with the Applied Biosystem real-time Prism 7900HT Sequence Detection System.

Results

The rs2241766 (TG + GG) [Odds ratio(95% Confidence Interval = 1.35(1.01-1.72); p = 0.015] and rs9842733A > T [1.48(1.01-2.07); p = 0.042] were associated with hypertension [HTN; 3541 cases vs 1101 controls), following adjustment for the presence of other cardiovascular risk traits. The rs2241766 (TG + GG) was further implicated in harbouring of low high density lipoprotein levels (LHDL; 1353 versus 2156 controls) [1.35(1.10-1.67); p = 0.005], but lost its association with obesity after the adjustment for confounders. Besides, low high density lipoprotein was also linked with rs6444174 (TC + CC) [1.28(1.05-1.59)]. On the other hand, while initial univariate logistic regression analysis pointed to rs1063537 C > T (p = 0.010), rs2082940 C > T (p = 0.035) and rs1063539 G > C (p = 0.035) as being associated with myocardial infarction, significance levels of these relationships were diminished following adjustment for the influence of confounding covariates. Interestingly, haplotyping showed that an 8-mer haplotype GTGCCTCA and several of its derivatives constructed from the studied SNPs were commonly implicated in MI (χ2 = 4.12; p = 0.042), HTN (χ2 = 6.40; p = 0.011) and OBS (χ2 = 5.18; p = 0.023).

Conclusion

These results demonstrate that the ADIPOQ 3′UTR harbours common susceptibility variants for metabolic risk traits and CAD, pointing to the importance of this region in atherosclerosis disease pathways.
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Literature
1.
go back to reference Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC: Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; national heart, lung, and blood institute; american heart association; world heart federation; international atherosclerosis society; and international association for the study of obesity. Circulation. 2009, 120 (16): 1640-1645. 10.1161/CIRCULATIONAHA.109.192644.CrossRefPubMed Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC: Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; national heart, lung, and blood institute; american heart association; world heart federation; international atherosclerosis society; and international association for the study of obesity. Circulation. 2009, 120 (16): 1640-1645. 10.1161/CIRCULATIONAHA.109.192644.CrossRefPubMed
3.
go back to reference Soodini GR: Adiponectin and leptin in relation to insulin sensitivity. Metab Syndr Relat Disord. 2004, 2 (2): 114-123. 10.1089/met.2004.2.114.CrossRefPubMed Soodini GR: Adiponectin and leptin in relation to insulin sensitivity. Metab Syndr Relat Disord. 2004, 2 (2): 114-123. 10.1089/met.2004.2.114.CrossRefPubMed
4.
go back to reference Siitonen N, Pulkkinen L, Lindstrom J, Kolehmainen M, Eriksson JG, Venojarvi M, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Tuomilehto J, Uusitupa M: Association of ADIPOQ gene variants with body weight, type 2 diabetes and serum adiponectin concentrations: the finnish diabetes prevention study. BMC Med Genet. 2011, 12: 5-CrossRefPubMedPubMedCentral Siitonen N, Pulkkinen L, Lindstrom J, Kolehmainen M, Eriksson JG, Venojarvi M, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Tuomilehto J, Uusitupa M: Association of ADIPOQ gene variants with body weight, type 2 diabetes and serum adiponectin concentrations: the finnish diabetes prevention study. BMC Med Genet. 2011, 12: 5-CrossRefPubMedPubMedCentral
5.
go back to reference Suriyaprom K, Phonrat B, Namjuntra P, Harnroongroj T, Tungtrongchitr R: The -11377C > G adiponectin gene polymorphism alters the adiponectin concentration and the susceptibility to type 2 diabetes in Thais. Int J Vitam Nutr Res. 2010, 80 (3): 216-224. 10.1024/0300-9831/a000020.CrossRefPubMed Suriyaprom K, Phonrat B, Namjuntra P, Harnroongroj T, Tungtrongchitr R: The -11377C > G adiponectin gene polymorphism alters the adiponectin concentration and the susceptibility to type 2 diabetes in Thais. Int J Vitam Nutr Res. 2010, 80 (3): 216-224. 10.1024/0300-9831/a000020.CrossRefPubMed
6.
go back to reference Du J, Ye X, Li Q, Yu X, Cheng J, Ma J, Gao Y, Lu Y, Du W, Shi H, et al: Genetic variants in the ADIPOQ gene and the risk of metabolic syndrome: a case–control study of a Chinese Han population. Ann Hum Genet. 2012, 76 (2): 101-109. 10.1111/j.1469-1809.2012.00699.x.CrossRefPubMed Du J, Ye X, Li Q, Yu X, Cheng J, Ma J, Gao Y, Lu Y, Du W, Shi H, et al: Genetic variants in the ADIPOQ gene and the risk of metabolic syndrome: a case–control study of a Chinese Han population. Ann Hum Genet. 2012, 76 (2): 101-109. 10.1111/j.1469-1809.2012.00699.x.CrossRefPubMed
7.
go back to reference Li Y, Li X, Shi L, Yang M, Yang Y, Tao W, Shi L, Xiong Y, Zhang Y, Yao Y: Association of adiponectin SNP + 45 and SNP + 276 with type 2 diabetes in Han Chinese populations: a meta-analysis of 26 case–control studies. PLoS One. 2011, 6 (5): e19686-10.1371/journal.pone.0019686.CrossRefPubMedPubMedCentral Li Y, Li X, Shi L, Yang M, Yang Y, Tao W, Shi L, Xiong Y, Zhang Y, Yao Y: Association of adiponectin SNP + 45 and SNP + 276 with type 2 diabetes in Han Chinese populations: a meta-analysis of 26 case–control studies. PLoS One. 2011, 6 (5): e19686-10.1371/journal.pone.0019686.CrossRefPubMedPubMedCentral
8.
go back to reference Boumaiza I, Omezzine A, Rejeb J, Rebhi L, Rejeb NB, Nabli N, Abdelaziz AB, Bouslama A: Association between eight adiponectin polymorphisms, obesity, and metabolic syndrome parameters in Tunisian volunteers. Metab Syndr Relat Disord. 2011, 9 (6): 419-426. 10.1089/met.2011.0035.CrossRefPubMed Boumaiza I, Omezzine A, Rejeb J, Rebhi L, Rejeb NB, Nabli N, Abdelaziz AB, Bouslama A: Association between eight adiponectin polymorphisms, obesity, and metabolic syndrome parameters in Tunisian volunteers. Metab Syndr Relat Disord. 2011, 9 (6): 419-426. 10.1089/met.2011.0035.CrossRefPubMed
9.
go back to reference Boumaiza I, Omezzine A, Rejeb J, Rebhi L, Ben Rejeb N, Nabli N, Ben Abdelaziz A, Boughzala E, Bouslama A: Single-nucleotide polymorphisms at the adiponectin locus and risk of coronary artery disease in Tunisian coronaries. J Cardiovasc Med (Hagerstown). 2011, 12 (9): 619-624. 10.2459/JCM.0b013e328348f1f8.CrossRef Boumaiza I, Omezzine A, Rejeb J, Rebhi L, Ben Rejeb N, Nabli N, Ben Abdelaziz A, Boughzala E, Bouslama A: Single-nucleotide polymorphisms at the adiponectin locus and risk of coronary artery disease in Tunisian coronaries. J Cardiovasc Med (Hagerstown). 2011, 12 (9): 619-624. 10.2459/JCM.0b013e328348f1f8.CrossRef
10.
go back to reference Al-Daghri NM, Alkharfy KM, Alokail MS, Alenad AM, Al-Attas OS, Abdul Khader M, Sabico S, Albagha OM: Assessing the contribution of 38 genetic loci to the risk of type 2 diabetes in the Saudi Arabian population. Clin Endocrinol (Oxf). 2013, doi:10.1111/cen.12187 Al-Daghri NM, Alkharfy KM, Alokail MS, Alenad AM, Al-Attas OS, Abdul Khader M, Sabico S, Albagha OM: Assessing the contribution of 38 genetic loci to the risk of type 2 diabetes in the Saudi Arabian population. Clin Endocrinol (Oxf). 2013, doi:10.1111/cen.12187
11.
go back to reference Sabouri S, Ghayour-Mobarhan M, Moohebati M, Hassani M, Kassaeian J, Tatari F, Mahmoodi-kordi F, Esmaeili HA, Tavallaie S, Paydar R, et al: Association between 45 T/G polymorphism of adiponectin gene and coronary artery disease in an Iranian population. ScientificWorldJournal. 2011, 11: 93-101.CrossRefPubMed Sabouri S, Ghayour-Mobarhan M, Moohebati M, Hassani M, Kassaeian J, Tatari F, Mahmoodi-kordi F, Esmaeili HA, Tavallaie S, Paydar R, et al: Association between 45 T/G polymorphism of adiponectin gene and coronary artery disease in an Iranian population. ScientificWorldJournal. 2011, 11: 93-101.CrossRefPubMed
12.
go back to reference Cheong MY, Bang OS, Cha MH, Park YK, Kim SH, Kim YJ: Association of the adiponectin gene variations with risk of ischemic stroke in a Korean population. Yonsei Med J. 2011, 52 (1): 20-25. 10.3349/ymj.2011.52.1.20.CrossRefPubMed Cheong MY, Bang OS, Cha MH, Park YK, Kim SH, Kim YJ: Association of the adiponectin gene variations with risk of ischemic stroke in a Korean population. Yonsei Med J. 2011, 52 (1): 20-25. 10.3349/ymj.2011.52.1.20.CrossRefPubMed
13.
go back to reference Al-Daghri NM, Al-Attas OS, Alokail MS, Alkharfy KM, Hussain T: Adiponectin gene variants and the risk of coronary artery disease in patients with type 2 diabetes. Mol Biol Rep. 2012, 493: 3703-3708. Al-Daghri NM, Al-Attas OS, Alokail MS, Alkharfy KM, Hussain T: Adiponectin gene variants and the risk of coronary artery disease in patients with type 2 diabetes. Mol Biol Rep. 2012, 493: 3703-3708.
14.
go back to reference Ling H, Waterworth DM, Stirnadel HA, Pollin TI, Barter PJ, Kesaniemi YA, Mahley RW, McPherson R, Waeber G, Bersot TP, et al: Genome-wide linkage and association analyses to identify genes influencing adiponectin levels: the GEMS Study. Obesity (Silver Spring). 2009, 17 (4): 737-744. 10.1038/oby.2008.625.CrossRef Ling H, Waterworth DM, Stirnadel HA, Pollin TI, Barter PJ, Kesaniemi YA, Mahley RW, McPherson R, Waeber G, Bersot TP, et al: Genome-wide linkage and association analyses to identify genes influencing adiponectin levels: the GEMS Study. Obesity (Silver Spring). 2009, 17 (4): 737-744. 10.1038/oby.2008.625.CrossRef
15.
go back to reference Chiodini BD, Specchia C, Gori F, Barlera S, D’Orazio A, Pietri S, Crociati L, Nicolucci A, Franciosi M, Signorini S, et al: Adiponectin gene polymorphisms and their effect on the risk of myocardial infarction and type 2 diabetes: an association study in an Italian population. Ther Adv Cardiovasc Dis. 2010, 4 (4): 223-230. 10.1177/1753944710371483.CrossRefPubMed Chiodini BD, Specchia C, Gori F, Barlera S, D’Orazio A, Pietri S, Crociati L, Nicolucci A, Franciosi M, Signorini S, et al: Adiponectin gene polymorphisms and their effect on the risk of myocardial infarction and type 2 diabetes: an association study in an Italian population. Ther Adv Cardiovasc Dis. 2010, 4 (4): 223-230. 10.1177/1753944710371483.CrossRefPubMed
16.
go back to reference Zhao T, Zhao J: Genetic effects of adiponectin on blood lipids and blood pressure. Clin Endocrinol (Oxf). 2011, 74 (2): 214-222. 10.1111/j.1365-2265.2010.03902.x.CrossRef Zhao T, Zhao J: Genetic effects of adiponectin on blood lipids and blood pressure. Clin Endocrinol (Oxf). 2011, 74 (2): 214-222. 10.1111/j.1365-2265.2010.03902.x.CrossRef
17.
go back to reference Chen JM, Ferec C, Cooper DN: A systematic analysis of disease-associated variants in the 3′ regulatory regions of human protein-coding genes I: general principles and overview. Hum Genet. 2006, 120 (1): 1-21. 10.1007/s00439-006-0180-7.CrossRefPubMed Chen JM, Ferec C, Cooper DN: A systematic analysis of disease-associated variants in the 3′ regulatory regions of human protein-coding genes I: general principles and overview. Hum Genet. 2006, 120 (1): 1-21. 10.1007/s00439-006-0180-7.CrossRefPubMed
18.
go back to reference Chen JM, Ferec C, Cooper DN: A systematic analysis of disease-associated variants in the 3′ regulatory regions of human protein-coding genes II: the importance of mRNA secondary structure in assessing the functionality of 3′ UTR variants. Hum Genet. 2006, 120 (3): 301-333. 10.1007/s00439-006-0218-x.CrossRefPubMed Chen JM, Ferec C, Cooper DN: A systematic analysis of disease-associated variants in the 3′ regulatory regions of human protein-coding genes II: the importance of mRNA secondary structure in assessing the functionality of 3′ UTR variants. Hum Genet. 2006, 120 (3): 301-333. 10.1007/s00439-006-0218-x.CrossRefPubMed
19.
go back to reference Bertoia ML, Waring ME, Gupta PS, Roberts MB, Eaton CB: Implications of new hypertension guidelines in the United States. Hypertension. 2007, 58 (3): 361-366.CrossRef Bertoia ML, Waring ME, Gupta PS, Roberts MB, Eaton CB: Implications of new hypertension guidelines in the United States. Hypertension. 2007, 58 (3): 361-366.CrossRef
21.
go back to reference Kuzuya T, Nakagawa S, Satoh J, Kanazawa Y, Iwamoto Y, Kobayashi M, Nanjo K, Sasaki A, Seino Y, Ito C, et al: Report of the committee on the classification and diagnostic criteria of diabetes mellitus. Diabetes Res Clin Pract. 2002, 55 (1): 65-85. 10.1016/S0168-8227(01)00365-5.CrossRefPubMed Kuzuya T, Nakagawa S, Satoh J, Kanazawa Y, Iwamoto Y, Kobayashi M, Nanjo K, Sasaki A, Seino Y, Ito C, et al: Report of the committee on the classification and diagnostic criteria of diabetes mellitus. Diabetes Res Clin Pract. 2002, 55 (1): 65-85. 10.1016/S0168-8227(01)00365-5.CrossRefPubMed
22.
go back to reference Mellitus WECoD: WHO expert committee on diabetes mellitus: second report. World Health Organ Tech Rep Ser. 1980, 646: 1-80. Mellitus WECoD: WHO expert committee on diabetes mellitus: second report. World Health Organ Tech Rep Ser. 1980, 646: 1-80.
23.
go back to reference Alberti KG, Zimmet PZ: Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 1998, 15 (7): 539-553. 10.1002/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S.CrossRefPubMed Alberti KG, Zimmet PZ: Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 1998, 15 (7): 539-553. 10.1002/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO;2-S.CrossRefPubMed
24.
go back to reference Teuscher A, Jarrett RJ: Diabetes mellitus: diagnostic criteria. Recommendations of the European Diabetes Epidemiology Study Group (EDESG) concerning the Second Report of the WHO Expert Committee on Diabetes Mellitus. Diabet Med. 1984, 1 (4): 305-307. 10.1111/j.1464-5491.1984.tb01979.x.CrossRefPubMed Teuscher A, Jarrett RJ: Diabetes mellitus: diagnostic criteria. Recommendations of the European Diabetes Epidemiology Study Group (EDESG) concerning the Second Report of the WHO Expert Committee on Diabetes Mellitus. Diabet Med. 1984, 1 (4): 305-307. 10.1111/j.1464-5491.1984.tb01979.x.CrossRefPubMed
25.
go back to reference Mellitus ECotDaCoD: Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 2003, 26 (Suppl 1): S5-S20. Mellitus ECotDaCoD: Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 2003, 26 (Suppl 1): S5-S20.
26.
go back to reference Schaid DJ, Rowland CM, Tines DE, Jacobson RM, Poland GA: Score tests for association between traits and haplotypes when linkage phase is ambiguous. Am J Hum Genet. 2002, 70 (2): 425-434. 10.1086/338688.CrossRefPubMed Schaid DJ, Rowland CM, Tines DE, Jacobson RM, Poland GA: Score tests for association between traits and haplotypes when linkage phase is ambiguous. Am J Hum Genet. 2002, 70 (2): 425-434. 10.1086/338688.CrossRefPubMed
27.
go back to reference Lake SL, Lyon H, Tantisira K, Silverman EK, Weiss ST, Laird NM, Schaid DJ: Estimation and tests of haplotype-environment interaction when linkage phase is ambiguous. Hum Hered. 2003, 55 (1): 56-65. 10.1159/000071811.CrossRefPubMed Lake SL, Lyon H, Tantisira K, Silverman EK, Weiss ST, Laird NM, Schaid DJ: Estimation and tests of haplotype-environment interaction when linkage phase is ambiguous. Hum Hered. 2003, 55 (1): 56-65. 10.1159/000071811.CrossRefPubMed
28.
go back to reference Wu Y, Li Y, Lange EM, Croteau-Chonka DC, Kuzawa CW, McDade TW, Qin L, Curocichin G, Borja JB, Lange LA, et al: Genome-wide association study for adiponectin levels in Filipino women identifies CDH13 and a novel uncommon haplotype at KNG1-ADIPOQ. Hum Mol Genet. 2010, 19 (24): 4955-4964. 10.1093/hmg/ddq423.CrossRefPubMedPubMedCentral Wu Y, Li Y, Lange EM, Croteau-Chonka DC, Kuzawa CW, McDade TW, Qin L, Curocichin G, Borja JB, Lange LA, et al: Genome-wide association study for adiponectin levels in Filipino women identifies CDH13 and a novel uncommon haplotype at KNG1-ADIPOQ. Hum Mol Genet. 2010, 19 (24): 4955-4964. 10.1093/hmg/ddq423.CrossRefPubMedPubMedCentral
29.
go back to reference Pischon T, Pai JK, Manson JE, Hu FB, Rexrode KM, Hunter D, Rimm EB: Single nucleotide polymorphisms at the adiponectin locus and risk of coronary heart disease in men and women. Obesity (Silver Spring). 2007, 15 (8): 2051-2060. 10.1038/oby.2007.244.CrossRef Pischon T, Pai JK, Manson JE, Hu FB, Rexrode KM, Hunter D, Rimm EB: Single nucleotide polymorphisms at the adiponectin locus and risk of coronary heart disease in men and women. Obesity (Silver Spring). 2007, 15 (8): 2051-2060. 10.1038/oby.2007.244.CrossRef
30.
go back to reference Tabatabaei-Malazy O, Hasani-Ranjbar S, Amoli MM, Heshmat R, Sajadi M, Derakhshan R, Amiri P, Namakchian M, Rezazadeh E, Tavakkoly-Bazzaz J, et al: Gender-specific differences in the association of adiponectin gene polymorphisms with body mass index. Rev Diabet Stud. 2010, 7 (3): 241-246.PubMedPubMedCentral Tabatabaei-Malazy O, Hasani-Ranjbar S, Amoli MM, Heshmat R, Sajadi M, Derakhshan R, Amiri P, Namakchian M, Rezazadeh E, Tavakkoly-Bazzaz J, et al: Gender-specific differences in the association of adiponectin gene polymorphisms with body mass index. Rev Diabet Stud. 2010, 7 (3): 241-246.PubMedPubMedCentral
31.
go back to reference Ermolaeva MD: Synonymous codon usage in bacteria. Curr Issues Mol Biol. 2001, 3 (4): 91-97.PubMed Ermolaeva MD: Synonymous codon usage in bacteria. Curr Issues Mol Biol. 2001, 3 (4): 91-97.PubMed
32.
go back to reference Lynn DJ, Singer GA, Hickey DA: Synonymous codon usage is subject to selection in thermophilic bacteria. Nucleic Acids Res. 2002, 30 (19): 4272-4277. 10.1093/nar/gkf546.CrossRefPubMedPubMedCentral Lynn DJ, Singer GA, Hickey DA: Synonymous codon usage is subject to selection in thermophilic bacteria. Nucleic Acids Res. 2002, 30 (19): 4272-4277. 10.1093/nar/gkf546.CrossRefPubMedPubMedCentral
Metadata
Title
The 3′-UTR of the adiponectin Q gene harbours susceptibility loci for atherosclerosis and its metabolic risk traits
Authors
Nzioka Muiya
Mohammed Al-Najai
Asma I Tahir
Samar Elhawari
Daisy Gueco
Editha Andres
Nejat Mazhar
Nada Altassan
Brian F Meyer
Maie Alshahid
Nduna Dzimiri
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2013
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/1471-2350-14-127

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