Polymorphisms in Sex Hormone Metabolism Genes and Risk of Preeclampsia in Taiyuan, China

Objective: Aberrant synthesis and metabolism of sex hormone are likely to be associated with alterations in vascular function in preeclampsia (PE). The study aims to investigate whether single nucleotide polymorphisms (SNPs) in sex hormone-related genes are associated with PE. Method: We performed a nested case-control study including 436 pregnant women (203 PE and 233 healthy or normal pregnant women) to investigate associations between 96 SNPs in 28 sex hormone-related genes and risk of PE. Results:TXNRD2/COMT rs3788314 and SULT1A2/SULT1A1 rs4788073 were associated with an increased risk of PE overall (p trend = 0.004 and 0.003, respectively), early-onset PE (p trend = 0.007 and 0.009, respectively), and severe PE (p trend = 0.002 and 0.005, respectively). Additionally, CYP17A1 rs4919690 and rs4919687 and LHCGR rs10180731 were associated with an increased risk of severe PE (p trend = 0.005, 0.006, and 0.014, respectively), while GNRHR rs2630488 was associated with a decreased risk of severe PE (p trend = 0.014). We also observed that HSD17B3 rs8190512 was associated with a decreased risk of early-onset PE (p trend = 0.003). We observed strong linkage disequilibrium in SULF1 (rs10106958, rs7813987, and rs6990375). Conclusions: Our study suggested that genetic polymorphisms in TXNRD2/COMT, SULT1A2/SULT1A1, CYP17A1, HSD17B3, GNRHR, LHCGR, and SULF1 might play a role in PE, especially in early-onset PE and severe PE. Future studies are warranted to replicate the observed associations and their functional mechanisms.