Dataset Information

Are single nucleotide polymorphisms rs7903146 and rs12255372 in transcription factor 7-like 2 gene associated with an increased risk for gestational diabetes mellitus in Egyptian women?

ABSTRACT:

Background

Genetic variants in the transcription factor 7-like 2 (TCF7L2) gene are related with type 2 diabetes (T2D) and gestational diabetes mellitus (GDM) in various populations, but there are not enough statistics regarding GDM among Egyptian women. We aimed by this study to evaluate the effect of two polymorphisms of rs7903146 and rs12255372 in the TCF7L2 gene with the development of GDM among Egyptian women.

Results

We enrolled 114 pregnant women with normal glucose tolerance and 114 with GDM according to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) guidelines. We gathered records on blood pressure, body mass index (BMI), blood glucose level, hemoglobin A1C (HbA1c), and lipid profile. The genotyping of rs7903146 and rs12255372 polymorphisms was carried out using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). The statistical significance of prepregnancy BMI, fasting blood sugar (FBS), HbA1c, low-density lipoprotein (LDL), and total cholesterol (Tch) was higher, P < 0.001, in GDM women in comparison to pregnant women without GDM. CT and TT genotypes in rs7903146 SNP were 46.5% vs. 54%, P <0.04, OR; CI = 1.9 (1.0 to 3.78); TT carriers were 37.7% vs. 9.6%, P <0.001, OR (CI) = 8.9 (3.7–21.1), respectively. For the TCFL2 gene rs12255372 SNP, GT carriers were 48.2% vs. 39.5%, P= 0.004, OR (CI) = 2.3 (1.3–4.2), while TT carriers were 24.6% vs. 7.9%, P < 0.001, OR (CI) = 6 (2.5–14.3).

Conclusion

The study showed there is a significantly higher incidence of CT/TT genotypes in rs7903146 SNP and GT/TT genotypes in rs12255372 SNP in TCF7L2 gene among GDM women in comparison to healthy pregnant women (controls).

SUBMITTER: Shalabi T

PROVIDER: S-EPMC8560867 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThere are racial and ethnic differences in the prevalence of gestational diabetes mellitus (GDM). Prior meta-analyses included small samples and very limited non-Caucasian populations. Studies to determine the relationship between transcription factor 7 like-2 (TCF7L2) rs7903146 polymorphism and risk of GDM in Hispanics/Latinos are recently available. The present meta-analysis was to estimate the impact of allele variants of TCF7L2 rs7903146 polymorphism on GDM susceptibility in overall population and racial/ethnic subgroups.MethodsLiterature was searched in multiple databases including PubMed, Web of Science, EMBASE (Ovid SP), Airiti Library, Medline Complete, and ProQuest up to July 2015. Allelic frequency for TCF7L2 rs7903146 polymorphism in GDM and control subjects was extracted and statistical analysis was performed using Comprehensive Meta-Analysis (CMA) 2.0 statistical software. The association between TCF7L2 rs7903146 polymorphism and GDM risk was assessed by pooled odd ratios (ORs) using five gene models (dominant, recessive, homozygote, heterozygote, and allele). Stratified analysis based on race/ethnicity was also conducted. The between-study heterogeneity and contribution of each single study to the final result was tested by Cochran Q test and sensitivity analyses, respectively. Publication bias was evaluated using Egger's linear regression test.ResultsA total of 16 studies involving 4,853 cases and 10,631 controls were included in this meta-analysis. Significant association between the T-allele of rs7903146 and GDM risk was observed under all genetic models, dominant model (OR = 1.44, 95% CI = 1.19-1.74), recessive model (OR = 1.35, 95% CI = 1.08-1.70), heterozygous model (OR = 1.31, 95% CI = 1.12-1.53), homozygous model (OR = 1.67, 95% CI = 1.31-2.12), and allele model (OR = 1.31, 95% CI = 1.12-1.53). Stratified analysis by race/ethnicity showed a statistically significant association between rs7903146 polymorphism and susceptibility to GDM under homozygous genetic model (TT versus CC) among whites, Hispanics/Latinos and Asians. Sensitivity analysis showed that the overall findings were robust to potentially influential decisions of the 16 studies included. No significant evidence for publication bias was observed in this meta-analysis for overall studies and subgroup studies.ConclusionsThis meta-analysis showed that the T allele of TCF7L2 rs7903146 polymorphism was associated with susceptibility of GDM in overall population in white, Hispanic/Latino and Asian sub-groups. Asians with homozygous TT allele of rs7903146 polymorphism have highest risk of GDM (OR = 2.08) followed by Hispanics/Latinos (OR = 1.80) and whites (OR = 1.51). The highest and lowest frequency of T allele of rs7903146 was found in Malaysia and South Korea, respectively. Future studies are needed to profile genetic risk for GDM among high risk Asian and Pacific Islander subgroups.

Project description:BackgroundThis study investigated whether single nucleotide polymorphisms (SNPs) reported by previous genome-wide association studies (GWAS) to be associated with impaired insulin secretion, insulin resistance, and/or type 2 diabetes are associated with disposition index, the homeostasis model assessment of insulin resistance (HOMA-IR), and/or development of diabetes following a pregnancy complicated by gestational diabetes mellitus (GDM).MethodsSeventy-two SNPs were genotyped in 374 women with previous GDM from Southern Sweden. An oral glucose tolerance test was performed 1-2 years postpartum, although data on the diagnosis of diabetes were accessible up to 5 years postpartum. HOMA-IR and disposition index were used to measure insulin resistance and secretion, respectively.ResultsThe risk A-allele in the rs11708067 polymorphism of the adenylate cyclase 5 gene (ADCY5) was associated with decreased disposition index (beta = - 0.90, SE 0.38, p = 0.019). This polymorphism was an expression quantitative trait loci (eQTL) in islets for both ADCY5 and its antisense transcript. The risk C-allele in the rs2943641 polymorphism, near the insulin receptor substrate 1 gene (IRS1), showed a trend towards association with increased HOMA-IR (beta = 0.36, SE 0.18, p = 0.050), and the T-allele of the rs4607103 polymorphism, near the ADAM metallopeptidase with thrombospondin type 1 motif 9 gene (ADAMTS9), was associated with postpartum diabetes (OR = 2.12, SE 0.22, p = 0.00055). The genetic risk score (GRS) of the top four SNPs tested for association with the disposition index using equal weights was associated with the disposition index (beta = - 0.31, SE = 0.29, p = 0.00096). In addition, the GRS of the four SNPs studied for association with HOMA-IR using equal weights showed an association with HOMA-IR (beta = 1.13, SE = 0.48, p = 9.72874e-11). All analyses were adjusted for age, body mass index, and ethnicity.ConclusionsThis study demonstrated the genetic susceptibility of women with a history of GDM to impaired insulin secretion and sensitivity and, ultimately, to diabetes development.