Butt Christopher, Gladman Dafna, Rahman Proton
St. Clare's Mercy Hospital, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
J Rheumatol. 2006 Aug;33(8):1631-3.
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activation has been shown to play a role in suppressing angiogenesis and inflammation, both important pathological features of psoriatic arthritis (PsA). Given the potential physiological role for PPAR-gamma in PsA, we examined known coding polymorphisms in the PPAR-gamma gene in a Caucasian population.
PsA was diagnosed as an inflammatory arthritis in patients with psoriasis, in the absence of other etiologies for inflammatory arthritis. Control subjects were ascertained from the same population and were all Caucasian. DNA samples were genotyped for 4 PPAR-gamma variants by time-of-flight mass spectrometry using the Sequenom platform. All 4 single-nucleotide polymorphisms (SNP) were previously-reported coding variations, 3 of which caused an amino acid change: Pro12Ala (rs1801282), Pro40Ala (rs1805192), and Pro115Gln (rs1800571); the fourth SNP, C161T (rs3856806), was synonymous. All primers were designed using Sequenom SpectroDesigner software, and scanned using a mass spectrometry workstation.
Of the 4 SNP examined, Pro40Ala and Pro115Gln were found to be nonpolymorphic in our population. Minor allele frequency for patients with PsA and controls for Pro12Ala (G) were 9.0% vs 13.8% (p = 0.017) and for C161T (T) 10.7% vs 12.0% (p = 0.56), respectively. All genotypes satisfied Hardy-Weinberg equilibrium.
An association between PsA and a known coding SNP of the PPAR-gamma gene was observed in our Caucasian population. Further studies are now warranted for validation of our findings in an independent cohort.
过氧化物酶体增殖物激活受体γ(PPAR-γ)的激活已被证明在抑制血管生成和炎症中发挥作用,而血管生成和炎症是银屑病关节炎(PsA)的两个重要病理特征。鉴于PPAR-γ在PsA中潜在的生理作用,我们在白种人群中研究了PPAR-γ基因中已知的编码多态性。
PsA被诊断为患有银屑病且无其他炎症性关节炎病因的患者的炎症性关节炎。对照受试者来自同一人群,均为白种人。使用Sequenom平台通过飞行时间质谱对DNA样本进行4种PPAR-γ变体的基因分型。所有4个单核苷酸多态性(SNP)均为先前报道的编码变异,其中3个导致氨基酸改变:Pro12Ala(rs1801282)、Pro40Ala(rs1805192)和Pro115Gln(rs1800571);第四个SNP,C161T(rs3856806),是同义的。所有引物均使用Sequenom SpectroDesigner软件设计,并使用质谱工作站进行扫描。
在所检测的4个SNP中,发现Pro40Ala和Pro115Gln在我们的人群中无多态性。PsA患者和对照中Pro12Ala(G)的次要等位基因频率分别为9.0%对13.8%(p = 0.017),C161T(T)的次要等位基因频率分别为10.7%对12.0%(p = 0.56)。所有基因型均符合哈迪-温伯格平衡。
在我们的白种人群中观察到PsA与PPAR-γ基因的一个已知编码SNP之间存在关联。现在有必要进行进一步研究以在独立队列中验证我们的发现。