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Tag polymorphisms of solute carrier family 12 member 3 gene modify the risk of hypertension in northeastern Han Chinese

Abstract

Converging evidence suggests that the gene encoding solute carrier family 12 member 3 (SLC12A3) is a logical candidate involved in the underlying cause of hypertension. We therefore selected four tag polymorphisms (rs2304483, rs5804, rs8063291 and rs6499857) from SLC12A3 gene to investigate their individual and interactive associations with hypertension in northeastern Han Chinese. There were 1009 hypertensive patients and 756 normotensive controls. Data were analyzed by Haplo.Stats and multifactor dimensionality reduction (MDR) softwares, and risk estimates were expressed as odds ratio (OR) and 95% confidence interval (95% CI). Overall, there were significant differences in the genotype (P=0.002) and allele (P=0.002) distributions of rs5804 between patients and controls. Compared with the most common haplotype A-C-T-G, haplotype G-C-T-G that was overrepresented in controls (P<0.001) reduced the crude and adjusted risk of hypertension by 36% (OR 0.64; 95% CI 0.50–0.81; P<0.001) and 39% (OR 0.61; 95% CI 0.48–0.79; P<0.001), respectively. Further interaction analyses identified an overall best MDR model including rs5804 and body mass index (P=0.001), which was validated by logistic regression analysis. Taken together, our findings demonstrate a predominant role played by SLC12A3 gene rs5804 in determining hypertension risk among northeastern Han Chinese. Moreover, the interaction of this polymorphism with obesity can enhance risk prediction.

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Acknowledgements

This study received grants from the National Natural Science Foundation of China (grant no. 81000109 and 30900808), the Department of Education Science and Technology Research Project in Heilongjiang Province (grant no. 12521621), the Beijing New Star Program (grant no. Z111107054511072) and the Shanghai Rising Star Program (grant no. 11QA1405500).

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Correspondence to Y-F Wang or W-Q Niu.

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Wang, YL., Qi, Y., Bai, JN. et al. Tag polymorphisms of solute carrier family 12 member 3 gene modify the risk of hypertension in northeastern Han Chinese. J Hum Hypertens 28, 504–509 (2014). https://doi.org/10.1038/jhh.2013.134

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