To investigate the association between primary knee osteoarthritis (OA) and single nucleotide polymorphism (SNP) (A668G) of leptin receptor gene (LEPR) in the Ningxia Hui population. A case-control association study has been adopted in this thesis. The polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis were performed to investigate the SNP of A668G site within LEPR from 148 patients with knee OA and 155 controls (asymptomatic and radiographically negative) with matched age and gender among Ningxia Hui population. In addition, genotypes of LEPR were verified by direct sequence analysis on PCR products. The result indicates that allele and genotype frequencies (P=0.024 and 0.008, respectively) in LEPR SNP A668G were significantly different in the knee OA patients group and control group, and in the knee OA patients group, the serum levels of leptin decreased significantly (P<0.001) and the serum levels of soluble leptin receptor increased significantly (P<0.001) compared with control group. Therefore, LEPR SNP A668G is associated with susceptibility to knee OA, which would be used as the genetic marker in predicting the risk of knee OA and would be one of the candidate genes in early prevention and con-trol.
[1] Fitzgerald GK, Piva SR, Irrgang JJ. Reports of joint instability in knee osteoarthritis: its prevalence and relationship to physical function. Arthritis Rheum, 2004, 51(6): 941-946.
[2] Kang XZ, Fransen M, Zhang YQ, Li H, Ke Y, Lu M, Su S, Song XY, Guo Y, Chen J, Niu JB, Felson D, Lin JH. The high prevalence of knee osteoarthritis in a rural Chinese population: the Wuchuan osteoarthritis study. Arthritis Rheum, 2009, 61(5): 641-647.
[3] Valdes AM, Spector TD. Genetic epidemiology of hip and knee osteoarthritis. Nat Rev Rheumatol, 2011, 7(1): 23-32.
[4] Panoutsopoulou K, Southam L, Elliott KS, Wrayner N, Zhai G, Beazley C, Thorleifsson G, Arden NK, Carr A, Chapman K, Deloukas P, Doherty M, McCaskie A, Ollier WE, Ralston SH, Spector TD, Valdes AM, Loughlin J. Insights into the genetic architecture of osteoarthritis from stage 1 of the arcOGEN study. Ann Rheum Dis, 2011, 70(50): 864-867.
[5] Zhang YY, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature, 1994, 372(6505): 425-432.
[6] Dumond H, Presle N, Terlain B, Mainard D, Loeuille D, Netter P, Pottie P. Evidence for a key role of leptin in osteoarthritis. Arthris Rheum, 2003, 48(11): 3118-3129.
[7] Figenschau Y, Knutsen G, Shahazeydi S, Johansen O, Sveinbjörnsson B. Human articular chondrocytes express functional leptin receptors. Biochem Biophys Res Commun, 2001, 287(1): 190-197.
[8] Qin JH, Shi DQ, Dai J, Zhu LQ, Tsezou A, Jiang Q. Association of the leptin gene with knee osteoarthritis susceptibility in a Han Chinese population: a case-control study. J Hum Genet, 2010, 55(10): 704-706.
[9] Kellgren JH, Lawrence JS. Radiological assessment of rheumatoid arthritis. Ann Rheum Dis, 1957, 16(4): 485-493.
[10] Franek E, Nowak J, Safranow K, Adler G, Bińczak-Kuleta A, Ciechanowicz A, Wiecek A. G(-2548)A leptin gene polymorphism in obese subjects is associated with serum leptin concentration and bone mass. Pol Arch Med Wewn, 2010, 120(5): 175-180.
[11] Ku JH, Lee CK, Joo BS, An BM, Choi SH, Wang TH, Cho HL. Correlation of synovial fluid leptin concentrations with the severity of osteoarthritis. Clin Rheumatol, 2009, 28(12): 1431-1435.
[12] Zhang FM, Basinski MB, Beals JM, Briggs SL, Churgay LM, Clawson DK, DiMarchi RD, Furman TC, Hale JE, Hsiung HM, Schoner BE, Smith DP, Zhang XY, Wery JP, Schevitz RW. Crystal structure of the obese protein leptin-E100. Nature, 1997, 387(6629): 206-209.
[13] Chung WK, Power-Kehoe L, Chua M, Chu F, Aronne L, Huma Z, Sothern M, Udall JN, Kahle B, Leibel RL. Ex-onic and intronic sequence variation in the human leptin receptor gene (LEPR). Diabetes, 1997, 46(9): 1509-1511.
[14] Yiannakouris N, Yannakoulia M, Melistas L, Chan JL, Klimis-Zacas D, Mantzoros CS. The Q223R polymorphism of the leptin receptor gene is significantly associated with obesity and predicts a small percentage of body weight and body composition variability. J Clin Endocrinol Metab, 2001, 86(9): 4434-4439.
[15] Koh JM, Kim DJ, Hong JS, Park JY, Lee KU, Kim SY, Kim GS. Estrogen receptor alpha gene polymorphisms Pvu Ⅱ and Xba Ⅰ influence association between leptin receptor gene polymorphism (Gln223Arg) and bone min-eral density in young men. Eur J Endocrinol, 2002, 147(6): 777-783.
