Genetic variants in the glucocorticoid pathway genes and birth weight.

PURPOSE:The aim of this study was to examine associations between single nucleotide polymorphisms (SNPs) that tag genetic variation in the glucocorticoid pathways (particularly in maternal genes FKBP5, NR3C1, and CRHR1) and birth weight. METHODS:The Franconian Maternal Health Evaluation Study (FRAMES) recruited healthy pregnant women prospectively for the assessment of maternal and fetal health. Germline DNA was collected from 375 pregnant women. Nine SNPs in the above-mentioned genes were genotyped. After reconstruction of haplotypes for each gene, a linear regression model was applied to the data to describe the association between haplotypes and birth weight. RESULTS:Female sex in the newborn (compared to male) was associated with lower birth weight, whereas a later week of gestation, higher body mass index pre-pregnancy, and higher parity were associated with higher birth weight. No association with birthweight was shown for the haplotypes of the selected SNPs. CONCLUSIONS:In this cohort of healthy unselected pregnant women, the analyzed candidate haplotypes in FKBP5, NR3C1, and CRHR1 did not show any association with birth weight. This might be in line with several other studies that have found no influence of fetal polymorphisms in the glucocorticoid receptor gene or triggers of the maternal HPA axis such as stress and psychosocial problems on birth weight. However, the small sample size in this study and the lack of consideration of individual risk factors and levels of stress in this cohort needs to be taken into account when interpreting the results.

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