A combination of single nucleotide polymorphisms in the 3′untranslated region of HLA-G is associated with preeclampsia

Reduced expression of human leukocyte antigen-G (HLA-G) has been linked to onset of preeclampsia. Associations have also been reported between preeclampsia and single nucleotide polymorphisms (SNP) in the 3′-untranslated region (UTR) of the HLA-G gene. However, there are conflicting results between studies. This studied examined whether a SNP, by itself or in combination with other SNPs, in the 3′UTR of the HLA-G gene is associated with an increased risk of preeclampsia. Placenta samples were obtained from 47 preeclamptic and 68 control cases. DNA was extracted, and the 3′UTR was sequenced and analyzed for nine polymorphisms using different genetic models of inheritance. Four of these polymorphisms have never been analyzed for an association with preeclampsia. Disputing existing reports, preeclamptic cases were suggestively associated with a G/G-genotype at SNP +3187 (p < 0.05). Several SNP combinations were more prevalent in preeclampsia cases. Following corrections for multiple testing, one SNP combination (+3027C/C and +3187G/G) was significantly more prevalent in preeclampsia cases using co-dominant, additive, and dominant models (p < 0.001). Taken together with the current literature, the data suggests that HLA-G 3′UTR SNP-pair associations, and not individual SNPs, could be useful in a predictive test for the susceptibility to preeclampsia.