Genetic variants related to insulin metabolism are associated with gestational diabetes mellitus

• Published in: Gene Vol. 927; p. 148704
• Main Authors: Bhushan, Ravi, Haque, Shafiul, Gupta, Rakesh Kumar, Rani, Anjali, Diwakar, Amita, Agarwal, Sakshi, Tripathi, Anima, Dubey, Pawan K.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15-11-2024
• Subjects: ARMS-PCR; GDM; Genotyping; Hardy Weinberg; SNPs; FTO; T2DM; TCF7L2; IRS1; IGFBP2; ARMS; GDM; Genotyping; SNP; PPARG2; SNPs; OGTT; Hardy Weinberg; ARMS-PCR
• ISSN: 0378-1119; 1879-0038; 1879-0038
• DOI: 10.1016/j.gene.2024.148704

•Associations of common genetic risk variants with GDM risk in the north Indian population were investigated.•Relative risk, population penetrance and attributable risk for risk allele variants was higher in GDM mother.•Four variants FTO, PPARG2, SLC30A8, and TCF7L2 were significantly associated with BMI, HbA1c and insulin.•Four variants FTO, PPARG2, SLC30A8, and TCF7L2 were significantly associated with GDM in North Indian population.
The current study sought to investigate the associations of common genetic risk variants with gestational diabetes mellitus (GDM) risk in the north Indian population and to evaluate their utility in identifying GDM cases. A case-control study, including 300 pregnant women, was included, and clinical and pathological information was collected. The amplification-refractory mutation system (ARMS) was used for genotyping four single nucleotide polymorphisms (SNPs), namely FTO (rs9939609), PPARG2 (rs1801282), SLC30A8 (rs13266634), and TCF7L2 (rs12255372). The odds ratio and confidence interval were determined for each SNP in different genetic models. Further, attributable risk, population penetrance, and relative risk were also calculated. The risk allele A of FTO (rs9939609) poses a two times higher risk of GDM (p = 0.02, OR = 2.5). The CG and GG genotypes of PPARG2 (rs1801282) have half a lower risk of GDM. In SLC30A8 (rs13266634), the recessive model analysis showed a two times higher risk of having GDM, while the recessive model (TT vs. GG + GT) analysis in TCF7L2 (rs12255372) indicates a lower risk of GDM. Finally, the relative risk, population penetrance, and attributable risk for risk allele in all four variants was higher in GDM mothers. All four polymorphisms were found to be significantly associated with BMI, HbA1c, and insulin. Our study first time confirmed a significant association with GDM for four variants, FTO, PPARG2, SLC30A8, and TCF7L2, in the North Indian population.