A cross-sectional study on the association of single nucleotide polymorphism of leptin receptor (Gln223Arg) and insulin resistance in gestational diabetes mellitus

Abstract

Background: The role of genetics in pathophysiology of gestational diabetes mellitus (GDM) is least explored. Objective of the study is to find the association of leptin receptor (LEPR) gene polymorphism with GDM and its role in altered leptin levels, insulin resistance, and dyslipidemia in GDM. Methods: Hundred GDM patients and an equal number of BMI and gestational age matched normal glucose tolerant pregnant women were recruited as cases and controls. Five milliliters of venous blood was drawn for biochemical and genetic analysis. Genotyping of LEPR (Gln223Arg) was performed by PCR-RFLP. Fasting blood sugar, leptin, insulin, C-peptide, and lipid profile estimations were done. Various insulin resistance models were constructed using suitable formulae. The statistical analysis was performed using SPSS 23.0 software. Results: There was no significant association found between LEPR gene polymorphism with leptin levels and insulin resistance in GDM. However, Odd’s ratio showed that individuals with the “A” allele were at 1.25 times higher risk of developing GDM. HOMA B-cell significantly varied among LEPR genotypes (p < 0.0001), values being double in AA genotype, compared to AG (p < 0.05), ten times higher in AA compared to GG (p < 0.0001). There was no significant deviation of the genotype frequency distributions for rs1137101 variants from HWE in GDM cases, suggesting that alleles were in equilibrium. Conclusion: The study established a cycle of gene polymorphism altering leptin levels which in turn can alter insulin secretion and insulin resistance, contributing to dyslipidemia of pregnancy as well as gestational diabetes.

Keywords

• Gestational diabetes mellitus
• Insulin resistance
• Hardy-weinberg equillibrium
• Leptin