Skip to main content
Top
Published in: BMC Medical Genetics 1/2018

Open Access 01-12-2018 | Research article

Possible association between ABCC8 C49620T polymorphism and type 2 diabetes in a Nigerian population

Authors: Godwill Azeh Engwa, Friday Nweke Nwalo, Claribel Chidimma Chikezie, Christie Oby Onyia, Opeolu Oyejide Ojo, Wilfred Fon Mbacham, Benjamin Ewa Ubi

Published in: BMC Medical Genetics | Issue 1/2018

Login to get access

Abstract

Background

The association between ABCC8 gene C49620T polymorphism and type 2 diabetes (T2D) in populations of diverse ethnic backgrounds has been reported. However, such occurrence in an African population is yet to be established. This case-control study involving 73 T2D and 75 non-diabetic (ND) patients investigated the occurrence of this polymorphism among T2D patients in Nigeria and assessed its relationship with body lipids of patients.

Methods

Demographic and clinical characteristics of patients were collected and lipid profile indices including total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and high density lipoprotein (HDL) were assayed. Restriction fragment length polymorphism-PCR (RFLP-PCR) was employed to genotype the ABCC8-C49620T polymorphism using PstI restriction enzyme.

Results

This study revealed significantly (p < 0.05) higher prevalence of the T allele of the ABCC8 gene in T2D patients (33.1%) compared to ND patients (28.0%). The mutant TT genotype was also higher than the CC and CT genotypes in T2D patients compared to ND patients but did not show any significant risk (p>0.05) of T2D for the unadjusted codominant, dominant and recessive models. Following age adjustment, the mutant genotypes (CT and TT) showed significant (p<0.05) risk of T2D for all the models with the recessive model presenting the greatest risk of T2D (OR: 2.39, 95% CI: 1.16-4.91, p<0.018). The TT genotype significantly (p<0.05) associated with high level of HDL and reduced levels of TC, TG and LDL in non-diabetic patients but was not associated with any of the demographic and clinical characteristics among T2D patients.

Conclusions

ABCC8 C49620T polymorphism showed possible association with T2D marked by predominance of the mutant TT genotype in T2D patients. However, the relationship between TT genotype and lipid abnormalities for possible beneficial effect on people suffering from T2D is unclear.
Literature
3.
go back to reference Das SK, Elbein SC. The genetic basis of type 2 diabetes. Cell science. 2:100–31. Das SK, Elbein SC. The genetic basis of type 2 diabetes. Cell science. 2:100–31.
4.
go back to reference Stumvoll M, Goldstein BJ, van Haeften TW. Type 2 diabetes: principles of pathogenesis and therapy. Lancet. 2005;365:1333–46.CrossRefPubMed Stumvoll M, Goldstein BJ, van Haeften TW. Type 2 diabetes: principles of pathogenesis and therapy. Lancet. 2005;365:1333–46.CrossRefPubMed
5.
go back to reference Aguilar-Bryan L, et al. Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion. Science. 1995;268(5209):423–6.CrossRefPubMed Aguilar-Bryan L, et al. Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion. Science. 1995;268(5209):423–6.CrossRefPubMed
6.
go back to reference Thomas PM, Cote GJ, Wohllk N, Haddad B, Mathew PM, Rabl W, Aguilar-Bryan L, Gagel RF, Bryan J. Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy. Science. 1995;268:426–9.CrossRefPubMed Thomas PM, Cote GJ, Wohllk N, Haddad B, Mathew PM, Rabl W, Aguilar-Bryan L, Gagel RF, Bryan J. Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy. Science. 1995;268:426–9.CrossRefPubMed
7.
go back to reference Goksel DL, Fischbach K, Duggirala R, Mitchell BD, Aguilar-Bryan L, Blangero J, Stern MP, O’Connell P. Variant in sulfonylurea receptor-1 gene is associated with high insulin concentrations in non-diabetic Mexican Americans: SUR-1 gene variant and hyperinsulinemia. Hum Genet. 1998;103:280–5.CrossRefPubMed Goksel DL, Fischbach K, Duggirala R, Mitchell BD, Aguilar-Bryan L, Blangero J, Stern MP, O’Connell P. Variant in sulfonylurea receptor-1 gene is associated with high insulin concentrations in non-diabetic Mexican Americans: SUR-1 gene variant and hyperinsulinemia. Hum Genet. 1998;103:280–5.CrossRefPubMed
8.
go back to reference Reis AF, Ye WZ, Dubois-Laforgue D, Bellanne-Chantelot C, Timsit J, Velho G. Association of a variant in exon 31 of the sulfonylurea receptor 1 (SUR1) gene with type 2 diabetes mellitus in French Caucasians. Hum Genet. 2000;107:138–44.CrossRefPubMed Reis AF, Ye WZ, Dubois-Laforgue D, Bellanne-Chantelot C, Timsit J, Velho G. Association of a variant in exon 31 of the sulfonylurea receptor 1 (SUR1) gene with type 2 diabetes mellitus in French Caucasians. Hum Genet. 2000;107:138–44.CrossRefPubMed
9.
go back to reference Altshuler D, Hirschhorn JN, Klannemark M, Lindgren CM, Vohl MC, Nemesh J, Lane CR, Schaffner SF, Bolk S, Brewer C, et al. The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nat Genet. 2000;26:76–80.CrossRefPubMed Altshuler D, Hirschhorn JN, Klannemark M, Lindgren CM, Vohl MC, Nemesh J, Lane CR, Schaffner SF, Bolk S, Brewer C, et al. The common PPARgamma Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nat Genet. 2000;26:76–80.CrossRefPubMed
10.
go back to reference Stefanski A, Majkowska L, Ciechanowicz A, et al. The common C49620T polymorphism in the sulfonylurea receptor gene (ABCC8), pancreatic beta cell function and long-term diabetic complications in obese patients with long-lasting type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes. 2007;115(5):317–21.CrossRefPubMed Stefanski A, Majkowska L, Ciechanowicz A, et al. The common C49620T polymorphism in the sulfonylurea receptor gene (ABCC8), pancreatic beta cell function and long-term diabetic complications in obese patients with long-lasting type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes. 2007;115(5):317–21.CrossRefPubMed
11.
go back to reference Florez JC, Jablonski KA, Kahn SE, Franks PW, Dabelea D, Hamman RF, Knowler WC, Nathan DM, Altshuler D. Type 2 diabetes–associated missense polymorphisms KCNJ11 E23K and ABCC8 A1369S influence progression to diabetes and response to interventions in the diabetes prevention program. Diabetes. 2007;56(2):531–6.CrossRefPubMedPubMedCentral Florez JC, Jablonski KA, Kahn SE, Franks PW, Dabelea D, Hamman RF, Knowler WC, Nathan DM, Altshuler D. Type 2 diabetes–associated missense polymorphisms KCNJ11 E23K and ABCC8 A1369S influence progression to diabetes and response to interventions in the diabetes prevention program. Diabetes. 2007;56(2):531–6.CrossRefPubMedPubMedCentral
14.
go back to reference Chen S, Lansdown AJ, Moat SJ, Ellis R, Goringe A, Dunstan FDJ, et al. An observational study of the effect of metformin on B12 status and peripheral neuropathy. Br J Diabetes Vascular Dis. 2012;12:189–93.CrossRef Chen S, Lansdown AJ, Moat SJ, Ellis R, Goringe A, Dunstan FDJ, et al. An observational study of the effect of metformin on B12 status and peripheral neuropathy. Br J Diabetes Vascular Dis. 2012;12:189–93.CrossRef
15.
go back to reference Trinder P. Determination of blood glucose using 4-aminophenazone as oxygen acceptor. J Clin Pathol. 1969;22(246):1–6. Trinder P. Determination of blood glucose using 4-aminophenazone as oxygen acceptor. J Clin Pathol. 1969;22(246):1–6.
16.
go back to reference Allain CC, Poon LS, Chan CS, Richmond W. Total cholesterol assay. Clin Chem. 1974;20:470–1.PubMed Allain CC, Poon LS, Chan CS, Richmond W. Total cholesterol assay. Clin Chem. 1974;20:470–1.PubMed
17.
go back to reference Esders TN, Michira CA. Triglyceride estimation. J Biol Chem. 1997;254:2710–2. Esders TN, Michira CA. Triglyceride estimation. J Biol Chem. 1997;254:2710–2.
18.
go back to reference Grove TH. Grove’s method of high density lipiptotein estimation. Clin Chem. 1979;25:560–2.PubMed Grove TH. Grove’s method of high density lipiptotein estimation. Clin Chem. 1979;25:560–2.PubMed
19.
go back to reference Friedwald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma without use of preparative Ultracenrifugation. Clin Chem. 1972;18:499–502. Friedwald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma without use of preparative Ultracenrifugation. Clin Chem. 1972;18:499–502.
20.
go back to reference He Y, Zhang R, Shao X, Hu C, Wang C, Lu J, Bao Y, JIa W, Xiang K. Association of KCNJ11 and ABCC8 genetic polymorphisms with response to repaglinide in Chinese diabetic patients. Acta Pharmacol Sin. 2008;29(8):983–9.CrossRefPubMed He Y, Zhang R, Shao X, Hu C, Wang C, Lu J, Bao Y, JIa W, Xiang K. Association of KCNJ11 and ABCC8 genetic polymorphisms with response to repaglinide in Chinese diabetic patients. Acta Pharmacol Sin. 2008;29(8):983–9.CrossRefPubMed
21.
go back to reference Engwa AG, Nwalo FN, Obi CE, Onyia C, Ojo OO, Mbacham WF, Ubi BE. Predominance of the a allele but no association of the KCNJ11 rs5219 E23K polymorphism with type 2 diabetes in a Nigerian population. Gen Mol Res. 2018;17(1):gmr16039889.CrossRef Engwa AG, Nwalo FN, Obi CE, Onyia C, Ojo OO, Mbacham WF, Ubi BE. Predominance of the a allele but no association of the KCNJ11 rs5219 E23K polymorphism with type 2 diabetes in a Nigerian population. Gen Mol Res. 2018;17(1):gmr16039889.CrossRef
22.
go back to reference Laukkanen O, Pihlajamaki J, Lindstrom J, Eriksson J, Valle T, Hamalainen H, et al. Polymorphisms of the SUR1 (ABCC8) and Kir6.2 (KCNJ11) genes predict the conversion from impaired glucose tolerance to type 2 diabetes. The Finnish diabetes prevention study. J Clin Endocrinol Metab. 2004;89:6286–90.CrossRefPubMed Laukkanen O, Pihlajamaki J, Lindstrom J, Eriksson J, Valle T, Hamalainen H, et al. Polymorphisms of the SUR1 (ABCC8) and Kir6.2 (KCNJ11) genes predict the conversion from impaired glucose tolerance to type 2 diabetes. The Finnish diabetes prevention study. J Clin Endocrinol Metab. 2004;89:6286–90.CrossRefPubMed
23.
go back to reference Pietrzak-Nowacka M, Safranow K, Bińczak-Kuleta A, Rózański J, Ciechanowski K, Ciechanowicz A. Association of C49620T ABCC8 polymorphism with anthropometric and metabolic parameters in patients with autosomal dominant polycystic kidney disease: a preliminary study. Nefrologia. 2012;32(2):153–9.PubMed Pietrzak-Nowacka M, Safranow K, Bińczak-Kuleta A, Rózański J, Ciechanowski K, Ciechanowicz A. Association of C49620T ABCC8 polymorphism with anthropometric and metabolic parameters in patients with autosomal dominant polycystic kidney disease: a preliminary study. Nefrologia. 2012;32(2):153–9.PubMed
24.
go back to reference Moleda P, Binczak-Kuleta A, Homa K, Safranow K, Celewicz Z, Syrenicz A, Stefanski A, Fronczyk A, Majkowska L. The common C49620T polymorphism in the sulfonylurea receptor gene SUR1 (ABCC8) in patients with gestational diabetes and subsequent glucose metabolism abnormalities. Exp Diabetes Res. 2012;2012:1–7.CrossRef Moleda P, Binczak-Kuleta A, Homa K, Safranow K, Celewicz Z, Syrenicz A, Stefanski A, Fronczyk A, Majkowska L. The common C49620T polymorphism in the sulfonylurea receptor gene SUR1 (ABCC8) in patients with gestational diabetes and subsequent glucose metabolism abnormalities. Exp Diabetes Res. 2012;2012:1–7.CrossRef
25.
go back to reference Yokoi N, Kanamori M, Horikawa Y, Takeda J, Sanke T, Furuta H, et al. Association studies of variants in the genes involved in pancreatic beta-cell function in type 2 diabetes in Japanese subjects. Diabetes. 2006;55:2379–86.CrossRefPubMed Yokoi N, Kanamori M, Horikawa Y, Takeda J, Sanke T, Furuta H, et al. Association studies of variants in the genes involved in pancreatic beta-cell function in type 2 diabetes in Japanese subjects. Diabetes. 2006;55:2379–86.CrossRefPubMed
26.
go back to reference Hart LM, De Knijff P, Dekker JM, et al. Variants in the sulphonylurea receptor gene: association of the exon 16- 3t variant with type II diabetes mellitus in Dutch Caucasians. Diabetologia. 1999;42(5):617–20.CrossRefPubMed Hart LM, De Knijff P, Dekker JM, et al. Variants in the sulphonylurea receptor gene: association of the exon 16- 3t variant with type II diabetes mellitus in Dutch Caucasians. Diabetologia. 1999;42(5):617–20.CrossRefPubMed
27.
go back to reference Rissanen J, Markkanen A, Karkkainen P, et al. Sulfonylurea receptor I gene variants are associated with gestational diabetes and type 2 diabetes but not with altered secretion of insulin. Diabetes Care. 2000;23(1):70–3.CrossRefPubMed Rissanen J, Markkanen A, Karkkainen P, et al. Sulfonylurea receptor I gene variants are associated with gestational diabetes and type 2 diabetes but not with altered secretion of insulin. Diabetes Care. 2000;23(1):70–3.CrossRefPubMed
28.
go back to reference Gloyn AL, Weedon MN, Owen KR, Turner MJ, Knight BA, Hitman G, et al. Large-scale association studies of variants in genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes. Diabetes. 2003;52:568–72.CrossRefPubMed Gloyn AL, Weedon MN, Owen KR, Turner MJ, Knight BA, Hitman G, et al. Large-scale association studies of variants in genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes. Diabetes. 2003;52:568–72.CrossRefPubMed
Metadata
Title
Possible association between ABCC8 C49620T polymorphism and type 2 diabetes in a Nigerian population
Authors
Godwill Azeh Engwa
Friday Nweke Nwalo
Claribel Chidimma Chikezie
Christie Oby Onyia
Opeolu Oyejide Ojo
Wilfred Fon Mbacham
Benjamin Ewa Ubi
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2018
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/s12881-018-0601-1

Other articles of this Issue 1/2018

BMC Medical Genetics 1/2018 Go to the issue