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Intragenic linkage disequilibrium structure of the human perilipin gene (PLIN) and haplotype association with increased obesity risk in a multiethnic Asian population

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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.

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Abbreviations

BMI :

Body mass index

CI :

Confidence interval

dNTP :

Deoxyribonucleoside triphosphate

LD :

Linkage disequilibrium

NHS 98 :

1998 Singapore National Health Survey

OR :

Odds ratio

PCR :

Polymerase chain reaction

SNP :

Single nucleotide polymorphism

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Acknowledgements

This study was supported by grants from the United States Department of Agriculture, Foreign Agricultural Service, International Cooperation and Development, Research and Scientific Exchanges Division, Scientific Cooperation Research Program, National Institutes of Health, National Heart, Lung, and Blood Institute grant HL-54776, contracts 53-K06-5-10 and 58-1950-9-001 from the United States Department of Agriculture Agricultural Research Service, National Medical Research Council of Singapore grant 0462/2000, and grants PR2004-0054 (to D.C.) from the Ministerio de Educación, Spain.

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Correspondence to Jose M. Ordovas.

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Qi, L., Tai, E.S., Tan, C.E. et al. Intragenic linkage disequilibrium structure of the human perilipin gene (PLIN) and haplotype association with increased obesity risk in a multiethnic Asian population. J Mol Med 83, 448–456 (2005). https://doi.org/10.1007/s00109-004-0630-4

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