title: A functional variant of NEDD4L is associated with obesity and related phenotypes in a Han population of Southern China.
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.
authors.affiliation: Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China. yxxzb@sohu.com.
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Wang
authors.forename: Hui-Ying
authors.initials: HY
authors.lastname: Liang
authors.forename: Yun-He
authors.initials: YH
authors.lastname: Gao
authors.forename: Xue-Ji
authors.initials: XJ
authors.lastname: Wu
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Bing-Ying
authors.initials: BY
authors.lastname: Pan
authors.forename: Xue-Xi
authors.initials: XX
authors.lastname: Yang
authors.forename: Hua-Zhang
authors.initials: HZ
authors.lastname: Liu
mesh_terms: D015992:Body Mass Index; D002681:China / Q000208:ethnology; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D000075702:Nedd4 Ubiquitin Protein Ligases; D009765:Obesity / Q000208:ethnology / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618485:Nedd4L protein, human; D044767:Ubiquitin-Protein Ligases
references.citation: Biochem J. 2005 Mar 15;386(Pt 3):461-70
references.pmid: 15496141
references.citation: Am J Physiol Renal Physiol. 2003 Nov;285(5):F916-29
references.pmid: 12876068
references.citation: J Am Coll Nutr. 2006 Jun;25(3 Suppl):247S-255S
references.pmid: 16772636
references.citation: Genetics. 1964 Jan;49(1):49-67
references.pmid: 17248194
references.citation: Hypertension. 2005 Sep;46(3):488-91
references.pmid: 16103266
references.citation: Obes Facts. 2011;4(1):67-75
references.pmid: 21372613
references.citation: Kidney Int. 2006 Aug;70(3):562-9
references.pmid: 16788695
references.citation: Am J Physiol Renal Physiol. 2005 Aug;289(2):F334-46
references.pmid: 15814530
references.citation: Hypertension. 2004 Oct;44(4):394-5
references.pmid: 15314034
references.citation: Clin Exp Hypertens. 2008 Feb;30(2):87-94
references.pmid: 18293164
references.citation: Curr Drug Targets. 2008 Aug;9(8):709-16
references.pmid: 18691017
references.citation: Bioinformatics. 2005 Jan 15;21(2):263-5
references.pmid: 15297300
references.citation: Hypertension. 2008 Mar;51(3):773-7
references.pmid: 18268134
references.citation: Am J Hum Genet. 2007 Feb;80(2):345-52
references.pmid: 17236139
references.citation: Diabetes. 2006 Dec;55(12):3411-7
references.pmid: 17130487
references.citation: Science. 2006 Jun 23;312(5781):1763-6
references.pmid: 16794074
references.citation: BMC Med Genet. 2009 Dec 09;10:130
references.pmid: 20003179
references.citation: Biochim Biophys Acta. 2010 Dec;1802(12):1166-77
references.pmid: 20347969
references.citation: J Hum Genet. 2002;47(12):665-76
references.pmid: 12522688
references.citation: Int J Mol Sci. 2012;13(7):8364-78
references.pmid: 22942708
references.citation: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2011 Oct;33(5):533-7
references.pmid: 22338138
references.citation: World J Gastroenterol. 2012 Jun 7;18(21):2719-26
references.pmid: 22690083
references.citation: Folia Biol (Praha). 2010;56(3):131-4
references.pmid: 20653998
references.citation: Bioinformatics. 2006 Aug 1;22(15):1928-9
references.pmid: 16720584
references.citation: Hypertension. 2009 Oct;54(4):796-801
references.pmid: 19635985
references.citation: Cell Death Differ. 2010 Jan;17(1):68-77
references.pmid: 19557014
references.citation: PLoS One. 2007 May 09;2(5):e432
references.pmid: 17487281
references.citation: Pflugers Arch. 2003 Jun;446(3):334-8
references.pmid: 12698368
references.citation: Diabetes. 2009 Dec;58(12):2828-34
references.pmid: 19741164
references.citation: Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2010 Dec;27(6):668-71
references.pmid: 21154329
references.citation: Am J Physiol Renal Physiol. 2001 Sep;281(3):F469-77
references.pmid: 11502596
references.citation: Mol Biol Rep. 2012 Oct;39(10):9557-62
references.pmid: 22740136
references.citation: Hypertens Res. 2010 May;33(5):386-93
references.pmid: 20442753
references.citation: PLoS Genet. 2011 Apr;7(4):e1001377
references.pmid: 21533078
references.citation: Curr Opin Cardiol. 1996 Sep;11(5):457-63
references.pmid: 8889370