title: A combination of single nucleotide polymorphisms in the 3'untranslated region of HLA-G is associated with preeclampsia.
abstract: 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.
authors.affiliation: The Create Fertility Centre, 790 Bay Street, Suite 1100, Toronto M5G 1N8, Canada. Electronic address: kevin@createivf.com.
authors.forename: K
authors.initials: K
authors.lastname: Quach
authors.affiliation: The Create Fertility Centre, 790 Bay Street, Suite 1100, Toronto M5G 1N8, Canada.
authors.forename: S A
authors.initials: SA
authors.lastname: Grover
authors.affiliation: The Create Fertility Centre, 790 Bay Street, Suite 1100, Toronto M5G 1N8, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Kenigsberg
authors.affiliation: The Create Fertility Centre, 790 Bay Street, Suite 1100, Toronto M5G 1N8, Canada; Department of Obstetrics and Gynecology, Sunnybrook Health Sciences Centre and Women's College Hospital, 2075 Bayview Avenue, Toronto M4N 3M5, Canada; Department of Obstetrics and Gynecology, University of Toronto, 563 Spadina Crescent, Toronto M5S 2J7, Canada.
authors.forename: C L
authors.initials: CL
authors.lastname: Librach
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000328:Adult; D001483:Base Sequence; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D059951:HLA-G Antigens / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D011225:Pre-Eclampsia / Q000235:genetics* / Q000276:immunology; D011247:Pregnancy; D017422:Sequence Analysis, DNA
chemical_list: D020413:3' Untranslated Regions; D059951:HLA-G Antigens
keywords: +3187A/G; 3′UTR; HLA-G; Preeclampsia; SNP