Association of Genetic Variants of Melatonin Receptor 1B with Gestational Plasma Glucose Level and Risk of Glucose Intolerance in Pregnant Chinese Women

Abstract

Background: This study aimed to explore the association of MTNR1B genetic variants with gestational plasma glucose homeostasis in pregnant Chinese women. Methods: A total of 1,985 pregnant Han Chinese women were recruited and evaluated for gestational glucose tolerance status with a two-step approach. The four MTNR1B variants rs10830963, rs1387153, rs1447352, and rs2166706 which had been reported to associate with glucose levels in general non-pregnant populations, were genotyped in these women. Using an additive model adjusted for age and body mass index (BMI), association of these variants with gestational fasting and postprandial plasma glucose (FPG and PPG) levels were analyzed by multiple linear regression; relative risk of developing gestational glucose intolerance was calculated by logistic regression. Hardy-Weinberg Equilibrium was tested by Chi-square and linkage disequilibrium (LD) between these variants was estimated by measures of D′ and \(r^2\). Results: In the pregnant Chinese women, the MTNR1B variant rs10830963, rs1387153, rs2166706 and rs1447352 were shown to be associated with the increased 1 hour PPG level (p = 8.04×10\(^{−10}\), 5.49×10\(^{−6}\), 1.89×10\(^{−5}\) and 0.02, respectively). The alleles were also shown to be associated with gestational glucose intolerance with odds ratios (OR) of 1.64 (p = 8.03×10\(^{−11}\)), 1.43 (p = 1.94×10\(^{−6}\)), 1.38 (p = 1.63×10\(^{−5}\)) and 1.24 (p = 0.007), respectively. MTNR1B rs1387153, rs2166706 were shown to be associated with gestational FPG levels (p = 0.04). Our data also suggested that, the LD pattern of these variants in the studied women conformed to that in the general populations: rs1387153 and rs2166706 were in high LD, they linked moderately with rs10830963, but might not linked with rs1447352;rs10830963 might not link with rs1447352, either. In addition, the MTNR1B variants were not found to be associated with any other traits tested. Conclusions: The MTNR1B is likely to be involved in the regulation of glucose homeostasis during pregnancy.