Maternal angiotensinogen (AGT) haplotypes, fetal renin (REN) haplotypes and risk of preeclampsia; estimation of gene-gene interaction from family-triad data

BMC Medical Genetics

Research Article

Hege K Vefring¹  Line Wee¹  Stein T Nilsen²  Rolv T Lie³  Astanand Jugessur⁴  Håkon K Gjessing⁵ 

[1] Department of Medical Biochemistry, Stavanger University Hospital, Stavanger, Norway;Department of Obstetrics and Gynecology, Stavanger University Hospital, Stavanger, Norway;Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway;Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway;Craniofacial Research, Musculoskeletal Disorders, Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Australia;Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway;Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway;

关键词: Preeclampsia;    Sudden Infant Death Syndrome;    Relative Risk Estimate;    Preeclamptic Woman;    Preeclamptic Pregnancy;   

DOI  :  10.1186/1471-2350-11-90

 received in 2010-01-20, accepted in 2010-06-10,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundPreeclampsia is a debilitating disorder affecting approximately 3% of pregnant women in the Western world. Although inconclusive, current evidence suggests that the renin-angiotensin system may be involved in hypertension. Therefore, our objective was to determine whether the genes for placental renin (REN) and maternal angiotensinogen (AGT) interact to influence the risk of preeclampsia.MethodsThree haplotype-tagging SNPs (htSNPs) covering REN (rs5705, rs1464818, and rs3795575) and another three covering AGT (rs2148582, rs2478545 and rs943580) were genotyped in 99 mother-father-child triads of preeclampsia pregnancies. We estimated relative risks (RR) conferred by maternal AGT and fetal REN haplotypes using HAPLIN, a statistical software designed to detect multi-marker transmission distortion among triads. To assess a combined effect of maternal AGT and fetal REN haplotypes, the preeclamptic triads were first stratified by presence/absence of maternal AGT haplotype C-T-A and tested for an effect of fetal REN across these strata.ResultsWe found evidence that mothers carrying the most frequent AGT haplotype, C-T-A, had a reduced risk of preeclampsia (RR of 0.4, 95% CI = 0.2-0.8 for heterozygotes and 0.6, 95% CI = 0.2-1.5 for homozygotes). Mothers homozygous for AGT haplotypes t-c-g and C-c-g appeared to have a higher risk, but only the former was statistically significant. We found only weak evidence of an overall effect of fetal REN haplotypes and no support for our hypothesis that an effect of REN depended on whether the mother carried the C-T-A haplotype of AGT (p = 0.33).ConclusionOur findings indicate that the mother's AGT haplotypes affect her risk for developing preeclampsia. However, this risk is not influenced by fetal REN haplotypes.

【 授权许可】

CC BY   
© Vefring et al; licensee BioMed Central Ltd. 2010