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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #176823
Title: INTRAGENIC LINKAGE DISEQUILIBRIUM STRUCTURE OF THE HUMAN PERILIPIN GENE (PLIN) AND HAPLOTYPE ASSOCIATED WITH INCREASED OBESITY RISK IN A MULTI-ETHNIC ASIAN POPULATION

Author
item QI, LU - TUFTS/HNRCA
item TAI, E - SINGAPORE GEN'L HOSPITAL
item TAN, CHEE - SINGAPORE GEN'L HOSPITAL
item SHEN, HAIQING - TUFTS/HNRCA
item CHEW, SUOK - SINGAPORE COLLEGE OF MED
item Greenberg, Andrew
item CORELLA, DOLORES - TUFTS/HNRCA
item Ordovas, Jose

Submitted to: Journal of Molecular Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/5/2004
Publication Date: 3/16/2005
Citation: Qi, L., Tai, E.S., Tan, C.E., Shen, H., Chew, S.K., Greenberg, A.S., Corella, D., Ordovas, J.M. 2005. Intragenic linkage disequilibrium structure of the human perilipin gene (PLIN) and haplotype associated with increased obesity risk in a multi-ethnic Asian population. Journal of Molecular Medicine. Available at http://springerlink.com (E-Pub) DOI: 10.1007/s00109-004-0630-4

Interpretive Summary: Obesity has been identified "one of today's most blatantly visible - yet most neglected - public health problems" This rising epidemic of overweight and obesity has been called by some as "globesity" to clearly reflect that is a global problem and that, unless action is taken, billions will suffer from debilitating conditions associated with this disorder. Overeating and sedentary lifestyle are major environmental factors determining the current globesity; however, genetic factors are also important to predispose some people to obesity, especially in some minority groups. However, we still know very little about the genetic component of obesity. We have examined the gene for perilipin, a protein that coats intracellular lipid droplets and modulates adipocyte lipolysis. We have evaluated the association between several polymorphisms at the perilipin gene and obesity-related phenotypes in 4,134 Asian subjects participating in a National Health Survey launched in Singapore. Our analysis demonstrated that, in women, polymorphisms at this gene were significantly associated with BMI in Indians and Malays. No significant associations between PLIN variations and obesity were found in men of any of the races investigated or in Chinese men and women. In summary, our previous data show that common mutations at the PLIN gene modulate body weight in white women. Moreover, the present report demonstrates that this effect is also present among Indian and Malay women.

Technical 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) in order to investigate their association with obesity risk. The study population consisted of 4,131 subjects of three ethnic groups (Chinese, Malay, and Indian) from Singapore. 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 females than in males. Crude analysis indicated that haplotype 11212 (CAAAT) was shared by both Malays and Asian Indians and was significantly associated with increased obesity risk as compared to the most common haplotype 21111 (TAGAA): OR=1.65, 95%CI 1.11-2.46 for Malays, and OR=1.94, 95%CI 1.06-3.53 for Indians. No associations between PLIN haplotypes and obesity risk were found in Chinese. In order to simplify the haplotype analyses, we used a subgroup of three SNPs (11482G>A, 13041A>G, and 14995A>T) in positive LD. These analyses revealed similar associations, showing that haplotypes XX212 (XXAAT) and XX222 (XXAGT) were associated with increased obesity risk in Malays (OR=2.04, 95%CI 1.28-3.25 and OR=2.05, 95%CI 1.35-3.12, respectively), and, that haplotype XXX212 (XXAAT) was 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 was 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 1.08-3.84). These results support the role of the PLIN locus as an ethnic dependent modulator of obesity risk in humans.