Association between carriers of TCF7L2 polymorphisms, insulin and glucagon-like peptide-1 among Arab pregnant women

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 806-823-Gestational Diabetes
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-808
Azza Khder1, Mooza Al-Khinji2, Randa Saleh2, Afsaneh Abdullah Rooshenas2 and Nasser M. Rizk*3
1Hammed Medical Corporation, 2Qatar University, 3Qatar University, Doha, Qatar
Background: The transcription factor TCF7L2 plays a fundamental factor for insulin secretion via glucagon-like peptide-1 (GLP-1) secretion. We studied the association between oral glucose tolerance response among pregnant women and circulating GLP-1, and insulin in carriers of TCF7L2polymorphisms.

Methods: A case control association study was performed on 268 Arab pregnant resident in Qatar at 26 weeks of gestation. We genotyped five single nucleotide polymorphisms in TCF7L2 (rs7903146, rs12255372, rs7901695, rs12243326, and rs11196205) by TaqMan assay. All participants underwent a 75 g oral glucose tolerance test (OGTT) for 3 hours for diagnosis of gestational diabetes mellitus “GDM”. GLP-1 and insulin were measured by Multiplex assay during the OGTT.

Results: Among the pregnant, 123 had GDM and 145 were controls. All SNPs were within the Hardy-Weinberg Equilibrium (HWE). The T was the minor allele for (rs7903146, rs12255372, and rs7901695) with a frequency of (0.379, 0.439 and 0.492) respectively, while C allele was the minor allele for (rs12243326, and rs11196205) with a frequency of (0.364) and (0.461), respectively. Using dominant genetic model, the Odds ratio and 95% CI for GDM was 1.98 (1.08-3.62), p=0.024 among T allele carriers of rs12255372 and was 2.02 (1.07-3.80), p=0.033 among G allele carriers of rs11196205 after controlling for age, BMI and insulin. Mean and SEM of serum insulin in (μU/ml) measured after 1h of OGTT was significantly lower in controls (262±36.45) vs. GDM (405.13±52.92), p=0.027, while mean and SEM of GLP-1 in (PM) measured after 1h of OGTT was insignificantly different between GDM (363.42±83.71) and controls (728.76±182.66), p=0.073.   Mean value and SEM of insulin (μU/ml), showed a significant different among subjects having TT+TG versus GG genotype of rs12255372 (524.97±77.22 Vs. 285.18 ±35.23, p= 0.003), and for subjects having GG+CG Vs. CC genotype of rs11196205 (482.61±44.25 Vs. 352.81± 61.42, p=0.045). No significant difference was observed for TT+TG versus GG genotype of rs12255372 and GG+CG vs. CC genotype of rs11196205 for GLP-1 among study subjects.

Conclusion: T allele carriers of rs12255372 and G allele carriers of rs11196205 may increase the risk of GDM among Arab pregnant women. Decreased insulin action among T allele and G allele carriers of rs12255372 and rs11196205 of TCF7L2, respectively may explain its role in the development of GDM, independent of GLP-1 effect.

Nothing to Disclose: AK, MA, RS, AA, NMR

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Sources of Research Support: The study was supported by a grant from HMC- Qatra and Qatar University.