Vitamin D metabolic loci and preeclampsia risk in multi‐ethnic pregnant women

Allelic variants in vitamin D metabolism genes may increase the risk of preeclampsia, but few studies have systematically tested this hypothesis. Our objective was to evaluate the relationship between maternal allelic variants in three vitamin D metabolism genes and risk of preeclampsia. Samples were from two case-control studies of pregnant women who delivered in Pittsburgh, PA from 1999 to 2010 and twelve recruiting sites across the United States from 1959 to 1965. Single-nucleotide polymorphisms (SNPs) were genotyped 50 kilobases up- and down-stream in three genes (VDR, GC, and CYP27B1) in the samples from both studies, for a total of 744 preeclampsia cases and 2411 controls. Using multivariable logistic regression, we estimated the associations between allelic variation in each locus and preeclampsia risk by maternal race and study. Meta-analysis was used to estimate the association across race-study groups for each SNP. Minor allele of a noncoding region of the VDR gene was significantly associated with preeclampsia risk, which was verified in the meta-analysis [odds ratio (OR), 95% confidence intervals (CI)] after adjusting for multiple comparisons [rs12831006:1.5 (1.2, 2.0), P < 0.0001]. The meta-analysis identified associations for one intron GC variant [rs843010:1.4 (1.1, 1.9) P < 0.05] and two variants of the flanking region of GC [rs842991:1.5 (1.1, 2.0) P < 0.05; rs16846876:0.75 (0.58, 0.98) P < 0.05]. There were no statistically significant associations for CYP27B1 SNPs. Our results provide additional support for a biological role of vitamin D in preeclampsia.