We tested association of four single nucleotide polymorphisms (SNPs) of the vitamin D receptor gene (VDR) with age at surgical and natural menopause in a sample of Caucasians composed of 153 women with surgical and 260 with natural menopause. A significant association was observed between age at surgical menopause and two SNPs, rs1544410 (BsmI) and rs731236 (TaqI) (p < 0.05). For rs1544410, homozygotes of the minor allele, AA, had about two-fold higher risk of surgical menopause than homozygotes of the major allele, GG (95% confidence ratio (CI) 1.09-3.82). For rs731236, the CC subjects had a greater chance of surgical menopause than the TT subjects (odds ratio = 2.01, 95% CI 1.07-3.78). Since rs1544410 and rs731236 are in strong linkage disequilibrium, the haplotypes based on these two loci were also tested. The haplotype AC was highly significantly associated with age at surgical menopause (p = 0.008). Women with this haplotype had surgical menopause on average 2.8 years earlier than non-carriers. These results reveal the potential effect of the VDR gene on ovaries and uterus, and suggest that its SNPs can be used as predictors of genetic susceptibility for early surgical menopause and respective causal health problems.
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