| Perilipin is localized at the surface of the lipid droplet in adipocytes and steroid-producing cells and plays an important role in the regulation of triglyceride deposition and mobilization. Perilipin is a target site of protein kinase A (PKA), and non-phosphorylated Perilipin may act as a barrier to the hormone sensitive lipase (HSL) mediated lipolysis of TAGs in lipid droplets. However, after being activated by protein kinase A, Perilpin translocates away from the lipid droplet and allows hormone sensitive lipase to hydrolyze the adipocyte triglycerides. In humans, the Perilipin gene (PLIN) locates in the 15q26.1 of chromosomal, which is the neighborhood of previously reported susceptibility loci for obesity, diabetes and hypertriglyceridemia. PLIN generates four different products (Perilipin A, B, C, and D) due to differential splicing. Perilipin A is the most common isoform in human adipose tissue.The recent studies on human Perilipin mainly concentrate on two aspects. One aspect is to investigate whether PLIN polymorphisms are associated with metabolic syndrome including obesity, diabetes mellitus, and their related variables (anthropometric variables, plasma lipids and glucose). The other aspect is to investigate whether Perilipin protein and mRNA levels in human adipose tissue are associated with obesity and obesity-related phenotypes. In the previous studies, there are more than ten common single nucleotide polymorphisms (SNPs) measured at the Perilipin (PLIN) locus to investigate their association with obesity risk. rs2304795 (T/C) has been reported in the Singapore Malays, Indians and Chinese, American and Spaniard whites, and Korean. These studies indicated that rs2304795 (T/C) polymorphism was associated with obesity-related phenotypes in American and Spanish White women. Studies in the Han Chinese indicated that C allele frequency of PLIN rs23 04795 (T/C) polymorphism was 0.048 and rs2304795 (T/C) polymorphism was not associated with any obesity-related variables and C allele frequency in the study population (0.048) is far lower than that in the Singapore Chineses (0.296).The purposes of the current study are to learn the distribution of genotypes and to explore the association between common single-nucleotide polymorphisms (rs2304795 T/C) at the PLIN locus and obesity, as well as obesity related phenotypes, in the Chinese Han population.Materials and methodsA total of 992 participants over 18 years old were randomly selected by using cluster sampling method from two rural communities in Henan. Questionnaire interview, physical examination, biochemical measurement and genotyping of PLIN gene rs2304795 were done for all the study participants.Questionnaire interview included demographic characteristics, medical history, and behavior risk factors. Anthropometric measurements included height, weight, waist and hip circumferences, and blood pressure, which were taken using standard techniques. Laboratory measurements were FPG, TC, HDL-C, LDL-C, Apoal and ApoB. PCR-RFLP method was employed to determine the genotypes of PLIN rs2304795. One-way analysis of variance (ANOVA) was used to compare the average levels of obesity related measurements among populations with diffrent genotypes. Afteradjusted for gender, age, cigarette smoking, alcohol consumption, and exercise, analysisof covariance was employed to compare the average levels of obesity relatedmeasurements among populations with diffrent genotypes. After adjusted by gender,age, cigarette smoking, alcohol consumption, and exercise, logistic regression analysisOR and its 95% confidence interval were used to evaluate the associations betweendifferent genotypes and obesity, diabetes mellitus, hypertension, andhypertriglyceridemia. The SAS 9.13 statistical package was used to analyze data.Statistical significance was defined at the 5% level.ResultsA total of 992 participants (mean age 48.29 years, 414 men and 578 women)participated in the current study. The prevalence rates of overweight, general obesity,and abdominal obesity were 32.32%, 15.86%, and 48.28%, respectively. Theage-adjusted prevalence rates for the above corresponding measurements were 28.75%,13.71%, and 40.36%, respectively.Generally, for PLIN rs2304795 (T/C) polymorphism, the T allele frequency is 0.729andthe C allele frequency is 0.271.The T and C allele frequencies are 0.718 and 0.282,respectively, among men and the T and C allele frequencies are 0.737 and 0.263,respectively, among women. The difference of allele frequencies between men andwomen is not statistically significant for PLIN rs2304795 (T/C)polymorphism (x~2 =0.92, P=0.338).In all participants, the genotype frequencies of T/T, T/C and C/C are 54.36%, 37.12%,and 8.52%, respectively. The observed and expected genotype frequencies areconsistent with Hardy-Weinberg equilibrium by x~2 -test(x~2 =3.56, P=0.059).The differences of genotype distributions for PLIN rs2304795 (T/C) polymorphism arenot significant among different gender, BMI, WC, BP, FBS and lipid levels (all 0.05).Neither univariate nor multivariate analyses shows any significant association between the genotype groups of polymorphism rs2304795 (T/C) and continuous variables such as BMI, BP, FBS, or lipid levels in men, women, as well as all participants (all P≥0.05).Among all participants, univariate analysis indicates that, compared with T/C and C/C genotypes, OR and 95% confidence interval of having general obesity, abdominal obesity, hypertension, diabetes mellitus, and hypertriglyceridemia for carriers of T/T genotype are 0.94(0.66, 1.35), 1.05(0.81, 1.35), 0.86(0.65, 1.15), 1.35(0.92, 2.00), and 1.31(0.95, 1.80), respectively. After adjusted by gender, age, cigarette smoking, alcohol consumption, and exercise, OR and 95% confidence interval are 0.97(0.74, 1.27), 0.90(0.63,1.29), 0.85(0.62,1.17), 1.43, (0.95,2.15), and 1.31(0.93,1.85), respectively. Among men, univariate analysis indicates that, compared with T/C and C/C genotypes, OR and 95% confidence interval of having general obesity, abdominal obesity, hypertension, diabetes mellitus, and hypertriglyceridemia for carriers of T/T genotype are 0.97(0.53, 1.77), 1.12(0.76, 1.66), 0.86(0.55, 1.33), 1.26(0.69, 2.32), and 1.56(0.90, 2.71), respectively. After adjusted by gender, age, cigarette smoking, alcohol consumption, and exercise, compared with T/C and C/C genotypes, carriers of T/T genotype has higher risk of having high LDL-cholesterol, OR and 95% confidence interval is 1.90 (1.05, 3.42).Among women, univariate analysis indicates that, compared with T/C and C/C genotypes, OR and 95% confidence interval of having general obesity, abdominal obesity, hypertension, diabetes mellitus, and hypertriglyceridemia for carriers of T/T genotype are 0.92(0.58, 1.44), 0.98(0.71, 1.37), 0.87(0.59, 1.26), 1.41(0.85, 2.35), and 1.17(0.79, 1.75), respectively. After adjusted by gender, age, cigarette smoking, alcohol consumption, and exercise, OR and 95% confidence interval were 0.92(0.59, 1.44), 0.91(0.63, 1.30), 0.88(0.58,1.36), 1.43(0.84, 2.44), and 1.08(0.70, 1.67), respectively.Conclusions1. For PLIN rs2304795 (T/C) polymorphism, T/T is the most common genotype in the Chinese Han population.2. There is no genetic association between PLIN rs2304795 (T/C) polymorphism and obesity, hypertension, and diabetes mellitus in the study population.3. Compared with T/C and C/C genotypes, carriers of T/T genotype have higher risk of having high LDL-cholesterol in men.
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