Gender-specific association of a perilipin gene haplotype with obesity risk in a white population

被引:69
作者
Qi, L
Shen, H
Larson, I
Schaefer, EJ
Greenberg, AS
Tregouet, DA
Corella, D
Ordovas, JM
机构
[1] Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Nutr & Genom Lab, Boston, MA 02111 USA
[2] Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Lipid Metab Lab, Boston, MA 02111 USA
[3] Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Obes & Metab Lab, Boston, MA 02111 USA
[4] Hop La Pitie Salpetriere, INSERM, U525, Fac Med, Paris, France
[5] Univ Valencia, Dept Prevent Med, Genet & Mol Epidemiol Unit, E-46003 Valencia, Spain
来源
OBESITY RESEARCH | 2004年 / 12卷 / 11期
关键词
adipose; lipolysis; triacylglycerol; polymorphism; haplotype;
D O I
10.1038/oby.2004.218
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: Perilipin is a class of protein-coating lipid droplets in adipocytes and steroidogenic cells. Our purpose was to examine the association between common single-nucleotide polymorphisms (SNPs) at the perilipin (PLIN) locus and obesity, as well as related phenotypes, in unrelated American adults. Research Methods and Procedures: Four PLIN SNPs (PLIN 6209T>C, 11482G>A, 13041A>G, and 14995A>T) were typed in 734 white subjects (373 men and 361 Women) attending a residential lifestyle intervention program. The baseline anthropometric and biochemical measures were used. Obesity was defined as BMI greater than or equal to 30 kg/m(2). Results: Multivariate analysis demonstrated that, in women, two of the SNPs (13041A>G, and 14995A>T) were significantly associated with percentage body fat (p = 0.016 for 13041A>G and p = 0.010 for 14995A>T) and waist circumference (p = 0.020 for 13041A>G and p = 0.045 for 14995A>T). Moreover, haplotype analysis using these two SNPs indicated that haplotypes A/T and G/T were both associated with significantly increased obesity risk (odds ratio = 1.76, 95% confidence interval 1.07 to 2.90 for haplotype A/T, and odds ratio = 1.73, 95% confidence interval 1.06 to 2.82 for haplotype G/T) when compared with haplotype A/A. No significant associations between PLIN variations and obesity were found in men. Discussion: Our data support the hypothesis that the PLIN locus may be a significant genetic determinant for obesity risk in whites and that women are more sensitive to the genetic effects of perilipin than men.
引用
收藏
页码:1758 / 1765
页数:8
相关论文
共 33 条
[1]   Obesity in North America - An overview [J].
Allison, DB ;
Saunders, SE .
MEDICAL CLINICS OF NORTH AMERICA, 2000, 84 (02) :305-+
[2]   Insulin resistance in type 2 diabetes: role of fatty acids [J].
Arner, P .
DIABETES-METABOLISM RESEARCH AND REVIEWS, 2002, 18 :S5-S9
[3]  
Arner P, 2000, BRIT J NUTR, V83, pS9
[4]   Hunting for human obesity genes? Look in the adipose tissue! [J].
Arner, P .
INTERNATIONAL JOURNAL OF OBESITY, 2000, 24 (Suppl 4) :S57-S62
[5]   EFFECTS OF LIFE-STYLE MODIFICATION ON SERUM-LIPIDS [J].
BARNARD, RJ .
ARCHIVES OF INTERNAL MEDICINE, 1991, 151 (07) :1389-1394
[6]   HEREDITY AND BODY-FAT [J].
BOUCHARD, C ;
PERUSSE, L .
ANNUAL REVIEW OF NUTRITION, 1988, 8 :259-277
[7]  
Brasaemle DL, 1997, J LIPID RES, V38, P2249
[8]   Perilipin A increases triacylglycerol storage by decreasing the rate of triacylglycerol hydrolysis [J].
Brasaemle, DL ;
Rubin, B ;
Harten, IA ;
Gruia-Gray, J ;
Kimmel, AR ;
Londos, C .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (49) :38486-38493
[9]   Coordinated upregulation of oxidative pathways and downregulation of lipid biosynthesis underlie obesity resistance in perilipin knockout mice - A microarray gene expression profile [J].
Castro-Chavez, F ;
Yechoor, VK ;
Saha, PK ;
Martinez-Botas, J ;
Wooten, EC ;
Sharma, S ;
O'Connell, P ;
Taegtmeyer, H ;
Chan, L .
DIABETES, 2003, 52 (11) :2666-2674
[10]   Role of the DGAT gene C79T single-nucleotide polymorphism in french obese subjects [J].
Coudreau, SK ;
Tounian, P ;
Bonhomme, G ;
Froguel, P ;
Girardet, JP ;
Guy-Grand, B ;
Basdevant, A ;
Clément, K .
OBESITY RESEARCH, 2003, 11 (10) :1163-1167