A candidate gene study reveals association between a variant of the Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) gene and systemic sclerosis.
A candidate gene study reveals association between a variant of the Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) gene and systemic sclerosis.
复制标题
DOI：
10.1186/s13075-015-0641-2
复制
发表时间：
2015-05-19
影响因子：
4.9
通讯作者：
Hayes MG
中科院分区：
文献类型：
--
作者：
Marangoni RG;Korman BD;Allanore Y;Dieude P;Armstrong LL;Rzhetskaya M;Hinchcliff M;Carns M;Podlusky S;Shah SJ;Ruiz B;Hachulla E;Tiev K;Cracowski JL;Varga J;Hayes MG
多功能核受体过氧化物酶体增殖物激活受体γ (PPAR-γ)具有强大的抗纤维化作用，其表达和活性在系统性硬化症（SSc）患者中受损。我们研究了与SSc相关的PPAR-γ基因（PPARG）单核苷酸多态性（SNPs）。跨越PPARG的标签snp在欧洲血统的美国发现队列中进行基因分型，该队列包括152名SSc患者和450名对照，在欧洲队列（来自法国的1031名SSc患者和1014名对照）中复制了我们的顶级信号。分析临床参数和疾病严重程度以评估与PPARG变异的临床关联。在发现队列中，单个PPARG内含子SNP （rs10865710）与SSc相关（p = 0.010；比值比= 1.52 / C等位基因，95%置信区间1.10-2.08）。这种关联在法国验证队列中得到了重复（p = 0.052；每个C等位基因的优势比= 1.16,95%置信区间为1.00-1.35）。两个队列的荟萃分析显示有更强的关联证据（p = 0.002；每个C等位基因的优势比= 1.22,95%可信区间1.07-1.40）。在法国SSc队列中，rs10865710 C等位基因也与肺动脉高压相关（p = 0.002；每个C等位基因的优势比= 2.33,95%可信区间1.34-4.03）。PPAR变异与SSc易感性相关，这与PPAR-γ在SSc发病机制中的作用一致。本文的在线版本（doi:10.1186/ s130775 -015-0641-2）包含补充材料，可供授权用户使用。
The multifunctional nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ) has potent anti-fibrotic effects, and its expression and activity are impaired in patients with systemic sclerosis (SSc). We investigated PPAR-γ gene (PPARG) single nucleotide polymorphisms (SNPs) associated with SSc. Tag SNPs spanning PPARG were genotyped in a European ancestry US discovery cohort comprising 152 SSc patients and 450 controls, with replication of our top signal in a European cohort (1031 SSc patients and 1014 controls from France). Clinical parameters and disease severity were analyzed to evaluate clinical associations with PPARG variants. In the discovery cohort, a single PPARG intronic SNP (rs10865710) was associated with SSc (p = 0.010; odds ratio = 1.52 per C allele, 95% confidence interval 1.10-2.08). This association was replicated in the French validation cohort (p = 0.052; odds ratio = 1.16 per C allele, 95% confidence interval 1.00-1.35). Meta-analysis of both cohorts indicated stronger evidence for association (p = 0.002; odds ratio = 1.22 per C allele, 95% confidence interval 1.07-1.40). The rs10865710 C allele was also associated with pulmonary arterial hypertension in the French SSc cohort (p = 0.002; odds ratio = 2.33 per C allele, 95% confidence interval 1.34-4.03). A PPARG variant is associated with susceptibility to SSc, consistent with a role of PPAR-γ in the pathogenesis of SSc. The online version of this article (doi:10.1186/s13075-015-0641-2) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
4.5
作者：
Allanore Y;Saad M;Dieudé P;Avouac J;Distler JH;Amouyel P;Matucci-Cerinic M;Riemekasten G;Airo P;Melchers I;Hachulla E;Cusi D;Wichmann HE;Wipff J;Lambert JC;Hunzelmann N;Tiev K;Caramaschi P;Diot E;Kowal-Bielecka O;Valentini G;Mouthon L;Czirják L;Damjanov N;Salvi E;Conti C;Müller M;Müller-Ladner U;Riccieri V;Ruiz B;Cracowski JL;Letenneur L;Dupuy AM;Meyer O;Kahan A;Munnich A;Boileau C;Martinez M
通讯作者：
Martinez M
DOI：
10.1016/j.bbrc.2008.07.014
发表时间：
2008-09-19
影响因子：
3.1
作者：
Ghosh, Asish K.;Wei, Jun;Wu, Minghua;Varga, John
通讯作者：
Varga, John
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
4.8
作者：
Liu, Yu;Yuan, Zuyi;Ma, Aiqun
通讯作者：
Ma, Aiqun
影响因子：
--
作者：
Ghosh, AK;Bhattacharyya, S;Varga, J
通讯作者：
Varga, J