Jalil Syed Fazal, Ahmed Iltaf, Gauhar Zeeshan, Ahmed Mushtaq, Malik Javaid M, John Peter, Bhatti Attya
Atta-Ur-Rahman School of Applied Biosciences (ASAB), National University of Science and Technology (NUST), Islamabad, 44000, Pakistan,
Rheumatol Int. 2014 May;34(5):699-703. doi: 10.1007/s00296-013-2768-2. Epub 2013 Apr 30.
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) belongs to a receptor superfamily of ligand-activated transcription factors, encoded by PPARG gene. Role of PPARγ has been well established in variety of metabolic disorders and in regulation of inflammation. In the present study, we aimed to investigate the association of PPARG (Pro12Ala; rs1801282) in clinically definite Pakistani Rheumatoid Arthritis (RA) patients and matching controls. The genotypes of the Pro12Ala variant in the PPARG were determined in a sample of 300 Pakistanis, including 150 RA cases and 150 controls. The genotyping was performed using Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR) method, and the data was analyzed through Graphpad Prism 5 V software. Allele-specific primer set (two forward: PPARG-F1, PPARG-F2 and a common reverse primer: PPARG-R) was used for amplification, and the product was resolved on 2 % agarose gel. The CC (ProPro) genotype has higher frequency in controls than RA cases [75 (50.0 %) vs. 51 (34.0 %)], whereas the CG (ProAla) genotype has relatively same frequencies in both cases and controls [72 (48.0 %) vs. 70 (46.6 %)]. However, significantly higher frequency of GG (AlaAla) genotype was observed in cases [27 (18.0 %) vs. 5 (3.3 %); χ2 18.54; p < 0.0001]. Furthermore, the minor allele G has significantly higher allele frequency in cases having same trend and direction of association (OR 1.991(1.412-2.808); p < 0.0001). These observations suggest that Pro12Ala (rs1801282), a coding variant in the PPARG gene, is associated with Rheumatoid Arthritis in Pakistanis.
过氧化物酶体增殖物激活受体γ（PPAR-γ）属于配体激活转录因子的受体超家族，由PPARG基因编码。PPARγ在多种代谢紊乱和炎症调节中的作用已得到充分证实。在本研究中，我们旨在调查PPARG（Pro12Ala；rs1801282）在临床确诊的巴基斯坦类风湿性关节炎（RA）患者及匹配对照中的相关性。在300名巴基斯坦人的样本中确定了PPARG中Pro12Ala变体的基因型，其中包括150例RA患者和150名对照。使用扩增阻滞突变系统-聚合酶链反应（ARMS-PCR）方法进行基因分型，并通过Graphpad Prism 5 V软件分析数据。等位基因特异性引物组（两条正向引物：PPARG-F1、PPARG-F2和一条通用反向引物：PPARG-R）用于扩增，产物在2%琼脂糖凝胶上进行分离。CC（ProPro）基因型在对照中的频率高于RA患者[75（50.0%）对51（34.0%）]，而CG（ProAla）基因型在患者和对照中的频率相对相同[72（48.0%）对70（46.6%）]。然而，在患者中观察到GG（AlaAla）基因型的频率显著更高[27（18.0%）对5（3.3%）；χ2 18.54；p<0.0001]。此外，小等位基因G在具有相同关联趋势和方向的患者中的等位基因频率显著更高（OR 1.991（1.412 - 2.808）；p<0.0001）。这些观察结果表明，PPARG基因中的编码变体Pro12Ala（rs1801282）与巴基斯坦人的类风湿性关节炎相关。
