No evidence for association of insulin receptor substrate-1 Gly972Arg variant with type 2 diabetes mellitus in a mixed-ancestry population of South Africa

Vergotine, Zelda; Kengne, André Pascal; Erasmus, Rajiv T; Matsha, Tandi E.

doi:10.7196/samj.7419

Cited by 5 publications

(3 citation statements)

References 26 publications

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“…Although few number of T2DM susceptibility genes discovered through candidate gene, linkage analyses, and GWA studies elsewhere have been replicated in African studies [16][17][18][19][20][21] , it must also be emphasized that many other association studies failed to show significant and replicable findings [22][23][24] . Therefore in this study we investigated three genes, namely, TCF7L2, FTO, and ENPP1 as risk factors for T2DM in a South African ethnic population group of Mixed-ancestry (Coloureds) with a unique genetic architecture.…”

Section: Introductionmentioning

confidence: 99%

Contribution of ENPP1, TCF7L2, and FTO polymorphisms to type 2 diabetes in mixed ancestry ethnic population of South Africa

et al. 2016

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Background: Transcription factor 7-like 2 gene (TCF7L2), fat mass and obesity-associated gene (FTO), and ectonucleotide pyrophosphatase/phosphodiesterase gene (ENPP1) are known risk loci for type 2 diabetes (T2DM) mostly in European populations. Objectives: To assess the association of these genes with T2DM risk in a South African mixed-ancestry population. Methods: Five hundred and sixty six participants were genotyped for ENPP1-rs997509 and -rs1044498, FTO-9941349 and -rs3751812, TCF7L2-rs12255372 and -rs7903146 polymorphisms using Taqman genotyping assays and validated by automated sequencing to assess the association of the polymorphisms with cardiometabolic traits. Results: In logistic regression models adjusted for age, sex, body mass index (BMI) and insulin resistance, minor allele of rs997509 was associated with a higher risk of prevalent T2DM under a recessive model [odd ratio 4.60 (95% confidence interval: 1.07 to 19.86); p = 0.040].Under additive model, the rs7903146 [1.43 (1.00 to 2.04); p= 0.053] and rs9941349 [1.43 (1.00 to 2.04); p = 0.052] minor alleles showed marginally significant associations with a high risk of T2DM. However, only the rs7903146 alleles (p=0.011) and genotypes (p=0.025) distributions were statistically significantly different between diabetic and non-diabetic individuals. Conclusion: Our findings demonstrate that ENPP1, TCF7L2, and FTO may predispose to T2DM in the mixed-ancestry population.

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Section: Introductionmentioning

confidence: 99%

Contribution of ENPP1, TCF7L2, and FTO polymorphisms to type 2 diabetes in mixed ancestry ethnic population of South Africa

et al. 2016

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“…In contrast, a direct genetic basis, specifically carriage of Gly972Arg (the most common single-nucleotide polymorphism in the insulin receptor substrate (IRS1) gene), associated with a 25% increased risk for developing diabetes, does not account for the high prevalence of type 2 diabetes mellitus (T2DM) in the mixed-ancestry population of SA. In Vergotine et al's study, [3] the first of its kind in Africa, 237 participants (24.7%) had T2DM. The overall prevalence of IRS1 Gly972Arg was 7.9%, with a higher occurrence of the variant found in non-diabetics, and it was not associated with obesity, insulin resistance/sensitivity or T2DM.…”

Section: Insulin Receptor Substrate-1 Gly972arg Variant and Type 2 Dmmentioning

confidence: 93%

Editor's Choice

Seggie

2014

S Afr Med J

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“…Recently, we observed a higher frequency of the IRS-1 972Arg polymorphism in DM2 and GDM pregnant women, and also a direct link between this gene variant and obesity and insulin resistance [12]. Although several authors have demonstrated a relationship between the Gly972Arg polymorphism and diabetes, Vergotine et al [13] showed that the Gly972Arg polymorphism was not associated with obesity, insulin resistance/sensitivity, or DM2 in the South African population.…”

Section: Introductionmentioning

confidence: 99%

IRS-1 gene polymorphism and DNA damage in pregnant women with diabetes or mild gestational hyperglycemia

Gelaleti

Damasceno

Salvadori

et al. 2015

Diabetol Metab Syndr

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BackgroundPregnant women with mild gestational hyperglycemia present a high risk for hypertension and obesity, and appear to reproduce the model of metabolic syndrome in pregnancy, including hyperinsulinemia and insulin resistance. Diabetic patients have a higher frequency of the IRS-1 Gly972Arg variant and this polymorphism is directly related to insulin resistance and subsequent hyperglycemia. In diabetes, hyperglycemia and other associated factors generate reactive oxygen species that increase DNA damage. The aims of this study were to evaluate the presence of the IRS-1 Arg972 polymorphism in pregnant women with diabetes or mild gestational hyperglycemia, and in their newborns. Additionally, we evaluated the level of primary DNA damage in lymphocytes of Brazilian pregnant women and the relationship between the amount of genetic damage and presence of the polymorphism.MethodsA based on the oral glucose tolerance test (OGTT) results and on glycemic profiles (GP), as follows: non-diabetic group, mild gestational hyperglycemia (MGH) and diabetic group. Eighty-five newborns were included in the study. Maternal peripheral blood samples and umbilical cord blood samples (5–10 mL) were collected for genotyping by PCR-RFLP and for comet assays.ResultsThe prevalence of genotype Gly/Arg in pregnant women groups was not statistically significant. In newborns, the frequency of Gly/Arg was significantly higher in the MGH and diabetic groups than in the non-diabetic group. Taken together, groups IIA and IIB (IIA + IIB; diabetes) presented lower amounts of DNA damage than the non-diabetic group (p = 0.064). No significant association was detected between genetic damage and the presence of the Arg972 genotype in pregnant women.ConclusionThe polymorphism was more prevalent in newborns of diabetic and MGH women. We believe that it is necessary to increase the number of subjects to be examined in order to better determine the biological role of the Arg972 polymorphism in these patients. Despite being classified as low-risk, pregnant women with mild gestational hyperglycemia characterize a population of maternal and perinatal adverse outcomes, and that, together with their newborns, require better monitoring by professionals and health services.

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No evidence for association of insulin receptor substrate-1 Gly972Arg variant with type 2 diabetes mellitus in a mixed-ancestry population of South Africa

Cited by 5 publications

References 26 publications

Contribution of ENPP1, TCF7L2, and FTO polymorphisms to type 2 diabetes in mixed ancestry ethnic population of South Africa

Contribution of ENPP1, TCF7L2, and FTO polymorphisms to type 2 diabetes in mixed ancestry ethnic population of South Africa

Editor's Choice

IRS-1 gene polymorphism and DNA damage in pregnant women with diabetes or mild gestational hyperglycemia

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