[A study of parent-of-origin effect of single nucleotide polymorphisms of imprinted gene KCNQ1 on risk for hypertension].

Abstract

Objective: To understand the potential parent-of-origin effect (POE) of imprinted gene KCNQ1 on the risk for hypertension by using a family-based design. Methods: Probands and their relatives in 9 rural areas in Fangshan District, Beijing, were included in this study. Mixed-effects model was used to evaluate the association between single nucleotide polymorphisms (SNPs) in the KCNQ1 gene and hypertension. The POE effects were evaluated by adopting log-linear model, and the interactions between POE and environmental factors, including smoking, alcohol consumption, were analyzed by using Wald χ² test. The POE was assessed by the ratio of maternal relative risk to paternal relative risk (RR_m/RR_f). Results: A total of 195 SNPs in the KCNQ1 gene were included in the analysis after quality control. The association analysis in 1 261 study participants identified 13 loci in the KCNQ1 gene associated with hypertension (all P<0.05). POE analysis, involving 167 study participants from 54 core families, identified 6 loci that showed possible POE with hypertension (all P<0.05). The most significant locus was rs231879, with an RR_m/RR_f of 3.46 (95%CI: 1.36-8.57, P=0.009), indicating that the relative risk of inheriting the risk allele from mother was 3.46 times higher than that from father. Analysis on the interactions between POE and environmental exposure revealed that sleep duration might potentially modify the POE of rs170786 (interaction for P=0.023). Conclusion: The imprinted gene KCNQ1 might be associated with the risk for hypertension through POE.