title: Association of Pro12Ala (rs1801282) variant of PPAR gamma with rheumatoid arthritis in a Pakistani population.
abstract: 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.
authors: Atta-Ur-Rahman School of Applied Biosciences (ASAB), National University of Science and Technology (NUST), Islamabad, 44000, Pakistan, syedfjalil@gmail.com.
authors: Syed Fazal
authors: SF
authors: Jalil
authors: Iltaf
authors: I
authors: Ahmed
authors: Zeeshan
authors: Z
authors: Gauhar
authors: Mushtaq
authors: M
authors: Ahmed
authors: Javaid M
authors: JM
authors: Malik
authors: Peter
authors: P
authors: John
authors: Attya
authors: A
authors: Bhatti
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D047495:PPAR gamma / Q000235:genetics*; D010154:Pakistan; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D047495:PPAR gamma
references: Neurosci Lett. 2009 Jan 2;449(1):81-3
references: 18977277
references: Nature. 2003 May 15;423(6937):356-61
references: 12748655
references: Diabetes. 2002 Aug;51(8):2341-7
references: 12145143
references: Biochem Biophys Res Commun. 2000 Apr 29;271(1):212-6
references: 10777704
references: Diabetologia. 2004 Mar;47(3):555-558
references: 14730381
references: Hepatology. 2003 Oct;38(4):1008-17
references: 14512888
references: Am J Physiol Gastrointest Liver Physiol. 2002 Aug;283(2):G266-9
references: 12121872
references: J Biol Chem. 2001 Nov 2;276(44):41245-54
references: 11533050
references: Diabetes. 2002 Aug;51(8):2653-7
references: 12145184
references: J Exp Med. 2001 Apr 2;193(7):827-38
references: 11283155
references: PLoS One. 2012;7(12):e53105
references: 23300871
references: J Clin Endocrinol Metab. 2002 Aug;87(8):3989-92
references: 12161548
references: Biochem Biophys Res Commun. 2000 Feb 5;268(1):178-82
references: 10652233
references: J Clin Invest. 1999 Aug;104(4):383-9
references: 10449430
references: Nature. 2000 May 25;405(6785):421-4
references: 10839530
references: Gastroenterology. 2008 Mar;134(3):688-95
references: 18325386
references: Arthritis Rheum. 2000 Jan;43(1):30-7
references: 10643697
references: J Mol Med (Berl). 2001;79(1):30-47
references: 11327101
references: J Clin Endocrinol Metab. 2004 Sep;89(9):4238-42
references: 15356014
references: Arthritis Rheum. 1988 Mar;31(3):315-24
references: 3358796
references: Rheumatol Int. 2006 Mar;26(5):388-92
references: 15988600
references: Nat Genet. 1998 Nov;20(3):284-7
references: 9806549
references: Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2009 Feb;26(1):87-90
references: 19199260
references: Arthritis Rheum. 1999 Jun;42(6):1071-9
references: 10366098
references: Pharmacol Rev. 2006 Dec;58(4):726-41
references: 17132851
references: Stroke. 2004 Sep;35(9):2036-40
references: 15284449