Variants in MODY genes associated with maternal lipids profiles in second trimester of pregnancy

Dyslipidemia during pregnancy increases the risk of complications of pregnancy. Lipid profiles have a strong genetic determinant and numerous susceptibility loci have been identified. However, very few studies have focused on the association of lipid-related loci and maternal serum lipids during pregnancy. For the first time, we investigated the association of common variants in three maturity onset diabetes of the young (MODY) genes (HNF1A, HNF4A and HNF1B) with serum lipid concentrations and glucose metabolism related quantitative traits in the second trimester of pregnancy.

A total of 1797 unrelated Han Chinese pregnant women were included. Three variants in 3'-UTR were selected and genotyped using TaqMan allelic discrimination assays. Multiple linear regression adjusted for age and body mass index was applied for analysis.

We found that T allele of rs1169309 in MODY3-HNF1A gene was significantly associated with increased levels of total cholesterol [β = 0.123 (0.057-0.189); p = 2.7 × 10^-4 ] and LDL-C [β = 0.075 (0.018-0.132); p = 1.0 × 10^-2 ]. Rs1169309-TT genotype carriers exhibited with higher levels of apolipoprotein A1 (p = 4.2 × 10^-2 ) and ApoB (p = 6.0 × 10^-3 ). In addition, correlations between minor C allele of HNF1B-rs2688 and decreased levels of HOMA-B (p = 1.4 × 10^-2 ), fasting insulin (p = 2.7 × 10^-2 ) and HOMA-IR (p = 3.8 × 10^-2 ) were identified. The minor C allele of HNF4A-rs6130615 was marginally associated with decreased fasting insulin levels (p = 0.050) and HOMA-IR (p = 0.048).

Variants in MODY genes playe a critical role in lipid and glucose homeostasis. Future studies will be required to further clarify the molecular mechanisms underlying these observed associations.