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Maternal-fetal HLA sharing and preeclampsia: variation in effects by seminal fluid exposure in a case-control study of nulliparous women in Iowa.

ABSTRACT: Whereas histocompatibility is critical for transplantation, HLA histoincompatibility is associated with successful pregnancy. Literature on HLA sharing and preeclampsia has been inconsistent; most studies focused on maternal-paternal rather than maternal-fetal sharing. This study examines whether maternal-fetal histocompatibility is associated with preeclampsia, and whether effects vary by semen exposure history. This case-control study of nulliparous women was designed to examine associations among HLA sharing, semen exposure, and preeclampsia. 258 preeclampsia cases and 182 normotensive controls met the eligibility criteria. HLA typing for mother and baby was performed for HLA-A, -B, -C, -DRB1, and -DQB1. We further restricted our study sample to 224 mother-baby pairs who had complete HLA typing for all five genes. Seminal fluid exposure indexes incorporated information on type of practice, frequency, contraceptive use (for vaginal exposure) and ingestion practices (for oral exposure). Multivariate models were adjusted for BMI and education. HLA-A matching, Class I matching, and combined Class I and II matching were associated with increased odds of preeclampsia. Among women with low semen exposure, effects of Class I matching were amplified (HLA-A matching, OR=6.27, 95%CI=1.04, 37.97; Class I matching, OR=4.49 per one-match increase, 95%CI=1.89, 14.50). With moderate to high semen exposure, Class II matching effects predominated (HLA-DQB1, OR=3.22, 95%CI=1.04, 9.99; Class II, OR=1.76 per one-match increase, 95%CI=1.05, 2.98; and total matches, OR=1.45 per one-match increase, 95%CI=1.02, 2.06). We found consistent evidence that maternal-fetal HLA sharing was associated with preeclampsia in a pattern influenced by prior vaginal exposure to paternal seminal fluid.

SUBMITTER: Triche EW

PROVIDER: S-EPMC4060772 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Maternal-fetal HLA sharing and preeclampsia: variation in effects by seminal fluid exposure in a case-control study of nulliparous women in Iowa.

Triche Elizabeth W EW Harland Karisa K KK Field Elizabeth H EH Rubenstein Linda M LM Saftlas Audrey F AF

Journal of reproductive immunology 20130806

Whereas histocompatibility is critical for transplantation, HLA histoincompatibility is associated with successful pregnancy. Literature on HLA sharing and preeclampsia has been inconsistent; most studies focused on maternal-paternal rather than maternal-fetal sharing. This study examines whether maternal-fetal histocompatibility is associated with preeclampsia, and whether effects vary by semen exposure history. This case-control study of nulliparous women was designed to examine associations a ...[more]

PMID: 23998333

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Project description:Preeclampsia is a leading cause of perinatal morbidity and mortality. This disorder is thought to be multifactorial in origin, with multiple genes, environmental and social factors, contributing to disease. One proposed mechanism is placental hypoxia-driven imbalances in angiogenic and anti-angiogenic factors, causing endothelial cell dysfunction. Catechol-O-methyltransferase (Comt)-deficient pregnant mice have a preeclampsia phenotype that is reversed by exogenous 2-methoxyestradiol (2-ME), an estrogen metabolite generated by COMT. 2-ME inhibits Hypoxia Inducible Factor 1?, a transcription factor mediating hypoxic responses. COMT has been shown to interact with methylenetetrahydrofolate reductase (MTHFR), which modulates the availability of S-adenosylmethionine (SAM), a COMT cofactor. Variations in MTHFR have been associated with preeclampsia. By accounting for allelic variation in both genes, the role of COMT has been clarified. COMT allelic variation is linked to enzyme activity and four single nucleotide polymorphisms (SNPs) (rs6269, rs4633, rs4680, and rs4818) form haplotypes that characterize COMT activity. We tested for association between COMT haplotypes and the MTHFR 677 C ? T polymorphism and preeclampsia risk in 1103 Chilean maternal-fetal dyads. The maternal ACCG COMT haplotype was associated with reduced risk for preeclampsia (P = 0.004), and that risk increased linearly from low to high activity haplotypes (P = 0.003). In fetal samples, we found that the fetal ATCA COMT haplotype and the fetal MTHFR minor "T" allele interact to increase preeclampsia risk (p = 0.022). We found a higher than expected number of patients with preeclampsia with both the fetal risk alleles alone (P = 0.052) and the fetal risk alleles in combination with a maternal balancing allele (P<0.001). This non-random distribution was not observed in controls (P = 0.341 and P = 0.219, respectively). Our findings demonstrate a role for both maternal and fetal COMT in preeclampsia and highlight the importance of including allelic variation in MTHFR.

Dataset Information

Maternal-fetal HLA sharing and preeclampsia: variation in effects by seminal fluid exposure in a case-control study of nulliparous women in Iowa.

Publications

Maternal-fetal HLA sharing and preeclampsia: variation in effects by seminal fluid exposure in a case-control study of nulliparous women in Iowa.

Similar Datasets

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