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A Functional Variant of NEDD4L Is Associated with Obesity and Related Phenotypes in a Han Population of Southern China
Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China
Guangzhou Women and Children Medical Center, Guangzhou 510623, China
School of Biotechnology, Southern Medical University, Guangzhou 510515, China
These authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 24 January 2013; in revised form: 15 March 2013 / Accepted: 25 March 2013 / Published: 2 April 2013
Abstract: NEDD4L is a candidate gene for hypertension, both functionally and genetically. Recently, studies showed evidence for the association of NEDD4L with obesity, a key intermediate phenotype in hypertension. To further investigate the relationship between NEDD4L and body mass-related phenotypes, we genotyped three common variants (rs2288774, rs3865418 and rs4149601) in a population-based study of 892 unrelated Han Cantonese using the Sequenom MALDI-TOF-MS platform. Allele frequencies and genotype distribution were calculated in lean controls and overweight/obese cases and analyzed for association by the Chi-squared test and Logistic regression. Linear regression analysis was used to analyze the effect of individual genotypes on quantitative traits. Multivariate analyses demonstrated that the minor allele of rs4149601(A = 20.9%) was associated with a 2.60 kg, 2.78 cm and 0.97 kg/m2 decrease per allele copy in weight, waist and BMI, respectively. Carriers of this allele also had a significant lower risk of overweight/obesity (p < 0.0001, OR = 0.52, 95% CI: 0.37–0.74) as compared to non-carriers. However, no significant association between genotypes at rs2288774 and rs3865418 and covariate-adjusted overweight/obesity or any related phenotypes was observed. These results suggested that the functional variant of NEDD4L, rs4149601, may be associated with obesity and related phenotypes, and further genetic and functional studies are required to understand its role in the manifestation of obesity.
Keywords: NEDD4L; genetic diversity; obesity
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Wang, Y.-L.; Liang, H.-Y.; Gao, Y.-H.; Wu, X.-J.; Chen, X.; Pan, B.-Y.; Yang, X.-X.; Liu, H.-Z. A Functional Variant of NEDD4L Is Associated with Obesity and Related Phenotypes in a Han Population of Southern China. Int. J. Mol. Sci. 2013, 14, 7433-7444.
Wang Y-L, Liang H-Y, Gao Y-H, Wu X-J, Chen X, Pan B-Y, Yang X-X, Liu H-Z. A Functional Variant of NEDD4L Is Associated with Obesity and Related Phenotypes in a Han Population of Southern China. International Journal of Molecular Sciences. 2013; 14(4):7433-7444.
Wang, Yu-Lin; Liang, Hui-Ying; Gao, Yun-He; Wu, Xue-Ji; Chen, Xi; Pan, Bing-Ying; Yang, Xue-Xi; Liu, Hua-Zhang. 2013. "A Functional Variant of NEDD4L Is Associated with Obesity and Related Phenotypes in a Han Population of Southern China." Int. J. Mol. Sci. 14, no. 4: 7433-7444.