Vimaleswaran K S, Radha V, Anjana M, Deepa R, Ghosh S, Majumder P P, Rao M R S, Mohan V
Madras Diabetes Research Foundation, Gopalapuram and Dr Mohan's Diabetes Specialities Centre, Chennai, India.
Int J Obes (Lond). 2006 Jun;30(6):884-91. doi: 10.1038/sj.ijo.0803228.
To evaluate whether polymorphisms in the peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PPARGC1A) gene were related to body fat in Asian Indians.
Three polymorphisms of PPARGC1A gene, the Thr394Thr, Gly482Ser and +A2962G, were genotyped on 82 type 2 diabetic and 82 normal glucose tolerant (NGT) subjects randomly chosen from the Chennai Urban Rural Epidemiology Study using PCR-RFLP, and the nature of the variants were confirmed using direct sequencing. Linkage disequilibrium (LD) was estimated from the estimates of haplotypic frequencies using an expectation-maximization algorithm. Visceral, subcutaneous and total abdominal fat were measured using computed tomography, whereas dual X-ray absorptiometry was used to measure central abdominal and total body fat.
None of the three polymorphisms studied were in LD. The genotype (0.59 vs 0.32, P=0.001) and allele (0.30 vs 0.17, P=0.007) frequencies of Thr394Thr polymorphism were significantly higher in type 2 diabetic subjects compared to those in NGT subjects. The odds ratio for diabetes (adjusted for age, sex and body mass index) for the susceptible genotype, XA (GA+AA) of Thr394Thr polymorphism, was 2.53 (95% confidence intervals: 1.30-5.04, P=0.009). Visceral and subcutaneous fat were significantly higher in NGT subjects with XA genotype of the Thr394Thr polymorphism compared to those with GG genotype (visceral fat: XA 148.2+/-46.9 vs GG 106.5+/-51.9 cm(2), P=0.001; subcutaneous fat: XA 271.8+/-167.1 vs GG 181.5+/-78.5 cm(2), P=0.001). Abdominal (XA 4521.9+/-1749.6 vs GG 3445.2+/-1443.4 g, P=0.004), central abdominal (XA 1689.0+/-524.0 vs GG 1228.5+/-438.7 g, P<0.0001) and non-abdominal fat (XA 18763.8+/-8789.4 vs GG 13160.4+/-4255.3 g, P<0.0001) were also significantly higher in the NGT subjects with XA genotype compared to those with GG genotype. The Gly482Ser and +A2962G polymorphisms were not associated with any of the body fat measures.
Among Asian Indians, the Thr394Thr (G --> A) polymorphism is associated with increased total, visceral and subcutaneous body fat.
评估过氧化物酶体增殖物激活受体γ共激活因子1α（PPARGC1A）基因多态性是否与亚洲印度人的体脂有关。
采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术，对从金奈城乡流行病学研究中随机选取的82例2型糖尿病患者和82例糖耐量正常（NGT）受试者的PPARGC1A基因的三个多态性位点Thr394Thr、Gly482Ser和+A2962G进行基因分型，并通过直接测序确认变异的性质。使用期望最大化算法从单倍型频率估计值中估计连锁不平衡（LD）。采用计算机断层扫描测量内脏、皮下和腹部总脂肪，而使用双能X线吸收法测量腹部中央和全身脂肪。
所研究的三个多态性位点均不存在连锁不平衡。与NGT受试者相比，2型糖尿病患者中Thr394Thr多态性的基因型频率（0.59对0.32，P = 0.001）和等位基因频率（0.30对0.17，P = 0.007）显著更高。Thr394Thr多态性的易感基因型XA（GA + AA）的糖尿病比值比（根据年龄、性别和体重指数调整）为2.53（95%置信区间：1.30 - 5.04，P = 0.009）。与GG基因型的NGT受试者相比，Thr394Thr多态性XA基因型的NGT受试者的内脏和皮下脂肪显著更高（内脏脂肪：XA 148.2±46.9对GG 106.5±51.9 cm²，P = 0.001；皮下脂肪：XA 271.8±167.1对GG 181.5±78.5 cm²，P = 0.001）。与GG基因型的NGT受试者相比，XA基因型的NGT受试者的腹部脂肪（XA 4521.9±1749.6对GG 3445.2±1443.4 g，P = 0.004）、腹部中央脂肪（XA 1689.0±524.0对GG 1228.5±438.7 g，P < 0.0001）和非腹部脂肪（XA 18763.8±8789.4对GG 13160.4±4255.3 g，P < 0.0001）也显著更高。Gly482Ser和+A2962G多态性与任何体脂测量指标均无关联。
在亚洲印度人中，Thr394Thr（G→A）多态性与全身、内脏和皮下体脂增加有关。
