CD36 fatty-acid-transporter gene variants-CD36 G/A (rs1761667) and CD36 C/T (rs75326924) as biomarkers for risk-prediction in gestational diabetes mellitus

CD36脂肪酸转运蛋白基因变异体——CD36 G/A (rs1761667) 和 CD36 C/T (rs75326924) 作为妊娠期糖尿病风险预测的生物标志物

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Abstract

BACKGROUND: Gestational diabetes mellitus (GDM) is a metabolic disorder causing hyperglycemia during pregnancy. Insulin resistance and decreased insulin secretion are linked to altered lipid metabolism that leads to progression of GDM. CD36 is a membrane glycoprotein involved in lipid metabolism and insulin sensitivity. Studies indicate that the CD36 gene is substantially linked to type 2 diabetes mellitus (T2DM) and could also influence GDM susceptibility. Insulin resistance and decreased insulin secretion are the hallmarks of T2DM, which is thought to have a similar genetic pathophysiology in GDM. AIM: To investigate the impact of CD36 gene polymorphisms [rs1761667 (G/A) and rs75326924 (C/T)] and mRNA expression in GDM women. METHODS: The case-control study involved a total of 400 pregnant women, (200 healthy controls and 200 GDM cases). The study of CD36 gene polymorphisms G/A (rs1761667) and C/T (rs75326924)) were determined by polymerase chain reaction-restriction fragment length polymorphism. The mRNA expression study of CD36 gene was analyzed by quantitative polymerase chain reaction/quantitative real-time polymerase chain reaction followed by statistical analysis done using GraphPad Prism8 software (ver. 8.0). RESULTS: The study revealed statistically significant association (P < 0.05) in anthropometric/biochemical parameters (age, gestational age, body mass index, fasting prandial glucose, post-prandial glucose, triglyceride, low-density lipoprotein) between GDM cases and healthy controls. CD36 G/A(rs1761667) and CD36 C/T (rs75326924) polymorphisms were significantly associated with GDM cases. The heterozygous genotypes (GA and CT) of both variants showed significant association (P = 0.0001 and P = 0.0025, odds ratio = 2.683 and 2.022 respectively). Allele frequency of 'T' allele in CD36 C/T (rs75326924) polymorphism was also found to be significant (P = 0.0046). CD36 gene was upregulated in individuals with GDM as compared to healthy controls (P = 0.0001). However, the upregulation of gene expression was not significantly associated with the genotypes of CD36 G/A (rs1761667) and CD36 C/T (rs75326924) polymorphisms. CONCLUSION: Heterozygous genotypes GA and CT of CD36 gene variants and expression are linked to GDM, potentially serving as predictive biomarkers for GDM susceptibility; further exploration needed in diverse ethnic communities.

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