Gender‐Specific Association of a Perilipin Gene Haplotype with Obesity Risk in a White Population

Abstract

QI, LU, HAIQING SHEN, ILONA LARSON, ERNST J. SCHAEFER, ANDREW S. GREENBERG, DAVID A. TREGOUET, DOLORES CORELLA, AND JOSE M. ORDOVAS. Gender-specific association of a perilipin gene haplotype with obesity risk in a white population. Obes Res. 2004;12:1758 -1765. 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 6209TϾC, 11482GϾA, 13041AϾG, and 14995AϾT) 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 Ն 30 kg/m 2 . Results: Multivariate analysis demonstrated that, in women, two of the SNPs (13041AϾG, and 14995AϾT) were significantly associated with percentage body fat (p ϭ 0.016 for 13041AϾG and p ϭ 0.010 for 14995AϾT) and waist circumference (p ϭ 0.020 for 13041AϾG and p ϭ 0.045 for 14995AϾT). 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 ϭ 1.76, 95% confidence interval 1.07 to 2.90 for haplotype A/T, and odds ratio ϭ 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.

Control of Adipose Triglyceride Lipase Action by Serine 517 of Perilipin A Globally Regulates Protein Kinase A-stimulated Lipolysis in Adipocytes

“…Consistent with this physiological function, Peri A polymorphisms and protein levels are associated with risk for obesity and insulin resistance (37,38). How Peri A regulates TAG storage and hydrolysis in adipocytes remains controversial (20,39).…”

Obesity and polymorphisms in genes regulating human adipose tissue

“…99 Additional intronic SNPs in the PLIN gene in women have been reported to be associated with obesity phenotypes. 100,101 Furthermore, PLIN 11482A carriers are resistant to weight loss following low-energy diets. 102 The mitochondrion and respiratory function in adipose tissue…”

Not Just Fat: The Structure and Function of the Lipid Droplet

“…Curiously the effect is more robust in females than in males, in both humans and mice (Qi et al 2004;Miyoshi et al 2010), but the reason for the gender difference is not known. It is also noteworthy that not only perilipin-null mice but also perilipin transgenic mice are resistant to diet-induced obesity (Qi et al 2004;Miyoshi et al 2010). These results reflect the multifaceted nature of perilipin function and suggest that obesity is a systemic disease caused by a combination of environmental and genetic factors.…”