Prevalence of the Pro12Ala missense mutation in the PPARG2 gene in Kuwaiti patients with primary knee osteoarthritis.
OBJECTIVE
Peroxisome proliferator-activated receptors (PPARs) play an important role in a number of cellular and metabolic functions. This study was carried out to determine the prevalence of a missense mutation (Pro12Ala) in the PPARG2 gene in Kuwaiti Arab patients with primary knee osteoarthritis (OA) and healthy controls with the aim of identifying a possible association.


METHODS
A prospective cross-sectional study carried out at three major teaching hospitals (referral centers) in the country over a one-year period.


METHODS
The prevalence of PPARG2 gene Pro12Ala missense mutation was determined in 104 Kuwaiti Arab patients with primary knee OA and 111 ethnically matched healthy controls. The prevalence of this Pro12Ala missense mutation was also determined in clinical subgroups of OA patients divided on the basis of age at onset, function and radiologic grading.


RESULTS
The Pro-Pro genotype of the PPARG2 gene Pro12Ala missense mutation was detected in 95/104 (91.3%) cases compared to 111/111 (100%) in the control subjects. The heterozygous Pro-Ala genotype was detected in 9/104 (8.7%) of the OA patients, while it was not detected in any of the controls. The Ala-Ala genotype was not detected in any of the OA patients or the controls. No significant differences were detected in the PPARG2 gene Pro12Ala genotypes in the subgroups of patients classified on the basis of age at onset, functional assessment using Lequesne's functional index, and radiological grading using Kellgren-Lawrence (K-L) grading.


CONCLUSIONS
This study found no significant association between the PPARG2 gene Pro12Ala missense mutation and knee OA. However, the presence of the Pro-Pro genotype of the PPARG2 gene mutation has a protective effect against development of OA.
Department of Pediatrics, Kuwait University, Faculty of Medicine, Jabriya, Kuwait.
Khaled F
KF
Al-Jarallah
Diaa K
DK
Shehab
Mohammad Z
MZ
Haider
D000368:Aged; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D006801:Humans; D007730:Kuwait; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D020370:Osteoarthritis, Knee / Q000235:genetics*; D047495:PPAR gamma / Q000235:genetics*; D011446:Prospective Studies
D047495:PPAR gamma
J Biol Chem. 2004 May 21;279(21):22057-65
15023995
J Rheumatol. 2002 Jan;29(1):3-14
11824967
Arthritis Rheum. 2001 Mar;44(3):595-607
11263774
Clin Exp Rheumatol. 2008 Mar-Apr;26(2):305-10
18565253
Endocr Rev. 2004 Dec;25(6):899-918
15583022
Autoimmun Rev. 2006 Apr;5(4):258-63
16697966
Ann Rheum Dis. 2006 Oct;65(10):1394-7
16973789
Osteoarthritis Cartilage. 2002 Feb;10(2):100-8
11869069
Osteoarthritis Cartilage. 2004;12 Suppl A:S39-44
14698640
J Clin Endocrinol Metab. 2000 May;85(5):1801-4
10843155
Arthritis Rheum. 2006 Feb;54(2):533-9
16453284
Biochem Biophys Res Commun. 1999 Jun 24;260(1):122-6
10381354
J Biol Chem. 2000 Apr 21;275(16):12243-50
10766862
Biochem Biophys Res Commun. 1997 Dec 18;241(2):270-4
9425261
Ann Rheum Dis. 1957 Dec;16(4):494-502
13498604
Arthritis Rheum. 1998 Aug;41(8):1343-55
9704632
Rheum Dis Clin North Am. 2002 Feb;28(1):95-109
11840700
Arthritis Rheum. 2005 Feb;52(2):479-87
15692987