Abstract
BackgroundThis study aimed to explore the association of MTNR1B genetic variants with gestational plasma glucose homeostasis in pregnant Chinese women.MethodsA 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 r2.ResultsIn 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.ConclusionsThe MTNR1B is likely to be involved in the regulation of glucose homeostasis during pregnancy.
Highlights
The number of women with gestational carbohydrate intolerance including gestational diabetes mellitus (GDM, glucose intolerance of any degree with onset or first recognition during pregnancy) is increasing world-wide and the prevalence varies considerably among racial and ethnic groups [1]
Several studies have examined the association of type 2 diabetes susceptibility loci with GDM [6,7,8,9], there is insufficient genetic evidence for the gestational carbohydrate intolerance; and so far, little knowledge is available regarding the predisposition of gestational carbohydrate homeostasis in pregnant Chinese women
After adjusting for age and body mass index (BMI), under the additive genetic model, each G allele of rs10830963 was found to be associated with an increased PPG level of 0.33 mmol/l
Summary
The number of women with gestational carbohydrate intolerance (abnormal oral glucose tolerance test results) including gestational diabetes mellitus (GDM, glucose intolerance of any degree with onset or first recognition during pregnancy) is increasing world-wide and the prevalence varies considerably among racial and ethnic groups [1]. Recent studies reported that adverse maternal-fetal outcomes were observed across the spectrum of carbohydrate intolerance including glucose values below current cutoffs for the diagnosis of GDM [2,3]. Both GDM and mild gestational carbohydrate intolerance in women may lead to a high risk of metabolic syndromes related to cardiovascular disease, type 2 diabetes, breast cancer and dementia later on in life [3,4]. This study aimed to explore the association of MTNR1B genetic variants with gestational plasma glucose homeostasis in pregnant Chinese women
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