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Trp64Arg polymorphism of the beta3-adrenergic receptor gene, pre-pregnancy obesity and risk of pre-eclampsia.

Zhang C, Williams MA, Edwards KL, Austin MA

Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle, WA, USA. nhcui@channing.harvard.edu

OBJECTIVE: Trp64Arg polymorphism of the beta3-adrenergic receptor (beta3-AR) gene was reported to be associated with increased risk of obesity and insulin resistance. Both traits have been implicated in the epidemiology and pathogenesis of pre-eclampsia. We investigated the relation of the beta3-AR gene to pre-pregnancy obesity and risk of pre-eclampsia. The present study is a case-control study of 87 Caucasian pre-eclampsia cases and 214 controls. METHODS: Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI), adjusted for maternal age and parity. Normotensive carriers of the variant allele (i.e. Arg64 allele) were 3.6 times more likely to be obese (body mass index (BMI) > or = 30 kg/m2) as compared with women not carrying the variant allele (OR = 3.6, 95% CI 0.8-15.0). RESULTS: Arg64 allele was more frequent in controls as compared with pre-eclampsia cases (11.7 vs. 5.3%, p < 0.01). After adjusting for age and parity, carriers experienced a 60% reduction in risk of pre-eclampsia (OR = 0.4, 95% CI 0.2, 0.9) as compared with women not carrying this allele. The association between carriage of the variant allele and risk of pre-eclampsia appeared to be modified by maternal BMI. Compared with lean carriers, lean women without the variant allele experienced only a small increase in the risk of pre-eclampsia (OR = 1.5; 95% CI: 0.6, 3.9). The OR for overweight women without the variant allele was 7.3 (95% CI 2.7-19.2). CONCLUSIONS: Our results suggest a puzzling relationship between the polymorphism and the risk of pre-eclampsia. Future studies are needed to confirm these findings.

Published 4 April 2005 in J Matern Fetal Neonatal Med, 17(1): 19-28.
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