title: Intragenic linkage disequilibrium structure of the human perilipin gene (PLIN) and haplotype association with increased obesity risk in a multiethnic Asian population.
abstract: Perilipin is a lipid droplet surface protein present in adipocytes and steroidogenic cells. We examined five common single nucleotide polymorphisms (SNPs) at the perilipin (PLIN) locus (PLIN 6209C>T, 10171A>T, 11482G>A, 13041A>G, and 14995A>T) to investigate their association with obesity risk. The study population included 4,131 subjects of three ethnic groups (Chinese, Malay, and Indian) from Singapore. The prevalence of obesity in Malays and Indians was much higher than in Chinese. Moreover, in these groups the prevalence of obesity was three times higher in women than in men. Crude analysis indicated that haplotype 11212 (CAAAT) is shared by Malays and Indians and is significantly associated with increased obesity risk as compared to the most common haplotype 21111 (TAGAA): OR 1.65 (95% CI 1.11-2.46) in Malays and 1.94 (95% CI 1.06-3.53) in Indians. No associations between PLIN haplotypes and obesity risk were found in Chinese. To simplify the haplotype analyses we used a subgroup of three SNPs (11482G>A, 13041A>G, and 14995A>T) in positive linkage disequilibrium. These analyses revealed similar associations, showing that haplotypes XX212 (XXAAT) and XX222 (XXAGT) are associated with increased obesity risk in Malays OR 2.04 (95% CI 1.28-3.25) and 2.05 (95% CI 1.35-3.12) respectively, and that haplotype XXX212 (XXAAT) is significantly associated with increased obesity risk in Indians OR 2.16 (95% CI 1.10-4.26) after adjusting for covariates including age, sex, smoking, alcohol consumption, exercise, and diabetes status. Moreover, individual SNP analyses demonstrated that the PLIN 14995A>T SNP is the most informative single genetic marker for the observed haplotype association, being significantly associated with increased obesity risk in both Malays OR 2.28 (95% CI 1.45-3.57) and Indians OR 2.04 (95% CI 1.08-3.64). These results support the role of the PLIN locus as an ethnically dependent modulator of obesity risk in humans.
authors.affiliation: Nutrition and Genomics Laboratory, Lipid Metabolism Laboratory, Jean Mayer-United States Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Qi
authors.forename: E Shyong
authors.initials: ES
authors.lastname: Tai
authors.forename: Chee Eng
authors.initials: CE
authors.lastname: Tan
authors.forename: Haiqing
authors.initials: H
authors.lastname: Shen
authors.forename: Suok Kai
authors.initials: SK
authors.lastname: Chew
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Greenberg
authors.forename: Dolores
authors.initials: D
authors.lastname: Corella
authors.forename: Jose M
authors.initials: JM
authors.lastname: Ordovas
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D002352:Carrier Proteins; D002681:China / Q000208:ethnology; D005260:Female; D008040:Genetic Linkage; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D007194:India / Q000208:ethnology; D015810:Linkage Disequilibrium / Q000235:genetics*; D008296:Malaysia / Q000208:ethnology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology / Q000235:genetics*; D016017:Odds Ratio; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012846:Singapore / Q000453:epidemiology
chemical_list: D002352:Carrier Proteins; D000070778:Perilipin-1; D010750:Phosphoproteins