197: Circadian clock genes and maternal glucose levels in pregnancy

Abstract

Circadian rhythms are observed in a wide range of physiological processes. Circadian genes have been associated with cardiovascular and metabolic derangements in both animal and human studies. Our objective was to use a candidate gene approach to determine if common genetic variants in circadian clock genes are associated with maternal glucose levels. Genotyping was performed on the Illumina 610 quad and 1M platforms as part of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. We examined 997 genotyped or imputed SNPs within 50 kb of circadian clock genes CLOCK, BMAL, CRY1, CRY2, PER1 and PER2 for their relationship with maternal glucose tolerance as assessed by a 75 gram oral glucose tolerance test (OGTT) at 28 weeks gestation in 1392 Northern European (NE), 841 Mexican Americans (MA) and 1148 Afro-Carib (AC) mothers from the HAPO cohort. We assessed the association between clock gene polymorphisms and maternal glucose using linear regression under an additive model, adjusting for field center, ancestry, maternal age, height, BMI and blood pressure, parity, gestational age at OGTT and neonatal gender. Several polymorphisms in CRY2 were associated with maternal 1-hr plasma glucose (1hPG) in NE mothers. The A allele of rs11605924 was associated with a higher 1hPG of 0.16 mg/dL per A-allele (s.e. 0.047; p=8.0 x 10-5). In MA mothers, several SNPs in CRY1 were associated with fasting plasma glucose (FPG) levels. Each copy of the T allele of rs10778528 was associated with lower FPG levels of 0.14 mg/dL (se 0.046; p=1.6 x 10-4). Data for the SNPs for all three ethnic-racial groups, as well as a mega-analysis (joint analysis of all three of the populations), are shown in the Table.Tabled 1 Common genetic variants in circadian clock genes may be associated with maternal glycemia in pregnancy. The different associations in the three populations may result from an interaction with unknown factors which differ between populations. Further studies are needed to examine how genetic and environmental alterations in circadian timing systems may impact maternal-fetal health.