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BMC Musculoskeletal Disorders
Published in: BMC Musculoskeletal Disorders 1/2016

Open Access 01-12-2016 | Research article

Association of rs1137101 polymorphism in LEPR and susceptibility to knee osteoarthritis in a Northwest Chinese Han population

Authors: Jianhui Yang, Heng Du, Jianguo Lv, Lianhe Zhang

Published in: BMC Musculoskeletal Disorders | Issue 1/2016

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Abstract

Background

Osteoarthritis (OA) is a complex arthritic condition in which the genetic factor plays a crucial role. A single nucleotide polymorphism (SNP), rs1137101 (Gln223Arg) of leptin receptor (LEPR) gene has been demonstrated to be associated with susceptibility to knee OA. However, this association in Chinese Han population has never been examined. The present study aimed to investigate whether Gln223Arg was related to knee OA susceptibility in a Northwest Chinese population with Han ethnicity.

Methods

Gln223Arg polymorphisms were genotyped in 587 patients with confirmed knee OA and in 628 age- and sex-matched healthy controls using polymerase chain reaction-restriction fragment length polymorphism analysis. Besides, LEPR genotypes were verified by direct DNA sequencing analysis on PCR products.

Results

The genotype and allele frequencies in LEPR SNP rs1137101 were significantly different between cases and control groups (chi-square = 6.52, P = 0.038 for genotype and chi-square = 5.06, P = 0.024 for allele frequencies; respectively). Rs1137101 was correlated with knee OA in the dominant genetic model (GG + GA versus AA) (P = 0.016) and a higher G allele frequency existed (P = 0.024) among all patients with knee OA and controls. On stratification analysis, the genotype GG and G allele were associated with susceptibility to knee OA in females, both young (≤65 years) and old groups (>65 years) and patients with mild knee OA.

Conclusions

Our finding suggested that the genetic variant of LEPR gene rs1137101 is independently related to knee OA susceptibility in Northwest Chinese population with Han ethnicity and may serve as a potential biomarker to determine risk of knee OA.
Literature
1.
Reginster JY. The prevalence and burden of arthritis. Rheumatology (Oxford). 2002;41(Supp 1):3–6.CrossRef
2.
Sun BH, Wu CW, Kalunian KC. New developments in osteoarthritis. Rheum Dis Clin North Am. 2007;33(1):135–48.CrossRefPubMed
3.
Xiang YJ, Dai SM. Prevalence of rheumatic diseases and disability in China. Rheumatol Int. 2009;29(5):481–90.CrossRefPubMed
4.
Spector TD, MacGregor AJ. Risk factors for osteoarthritis: genetics. Osteoarthritis Cartilage. 2004;12:S39–44.CrossRefPubMed
5.
Teichtahl AJ, Wluka AE, Proietto J, Cicuttini FM. Obesity and the female sex, risk factors for knee osteoarthritis that may be attributable to systemic or local leptin biosynthesis and its cellular effects. Med Hypotheses. 2005;65(2):312–5.CrossRefPubMed
6.
Valdes AM, Doherty S, Muir KR, Zhang W, Maciewicz RA, Wheeler M, Arden N, Cooper C, Doherty M. Genetic contribution to radiographic severity in osteoarthritis of the knee. Ann Rheum Dis. 2012;71(9):1537–40.CrossRefPubMedPubMedCentral
7.
8.
Dumond H, Presle N, Terlain B, Mainard D, Loeuille D, Netter P, Pottie P. Evidence for a key role of leptin in osteoarthritis. Arthritis Rheum. 2003;48(11):3118–29.CrossRefPubMed
9.
Simopoulou T, Malizos KN, Iliopoulos D, Stefanou N, Papatheodorou L, Ioannou M, Tsezou A. Differential expression of leptin and leptin’s receptor isoform (Ob-Rb) mRNA between advanced and minimally affected osteoarthritic cartilage; effect on cartilage metabolism. Osteoarthritis Cartilage. 2007;15(8):872–83.CrossRefPubMed
10.
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):1431–5.CrossRefPubMed
11.
Baumann H, Morella KK, White DW, Dembski M, Bailon PS, Kim H, Lai CF, Tartaglia LA. The full-length leptin receptor has signaling capabilities of interleukin 6-type cytokine receptors. Proc Natl Acad Sci U S A. 1996;93(16):8374–8.CrossRefPubMedPubMedCentral
12.
Figenschau Y, Knutsen G, Shahazeydi S, Johansen O, Sveinbjornsson B. Human articular chondrocytes express functional leptin receptors. Biochem Biophys Res Commun. 2001;287(1):190–7.CrossRefPubMed
13.
Portoles O, Sorli JV, Frances F, Coltell O, Gonzalez JI, Saiz C, Corella D. Effect of genetic variation in the leptin gene promoter and the leptin receptor gene on obesity risk in a population-based case–control study in Spain. Eur J Epidemiol. 2006;21(8):605–12.CrossRefPubMed
14.
Furusawa T, Naka I, Yamauchi T, Natsuhara K, Kimura R, Nakazawa M, Ishida T, Inaoka T, Matsumura Y, Ataka Y, et al. The Q223R polymorphism in LEPR is associated with obesity in Pacific Islanders. Hum Genet. 2010;127(3):287–94.CrossRefPubMed
15.
Quinton ND, Lee AJ, Ross RJ, Eastell R, Blakemore AI. A single nucleotide polymorphism (SNP) in the leptin receptor is associated with BMI, fat mass and leptin levels in postmenopausal Caucasian women. Hum Genet. 2001;108(3):233–6.CrossRefPubMed
16.
Brandl EJ, Frydrychowicz C, Tiwari AK, Lett TA, Kitzrow W, Buttner S, Ehrlich S, Meltzer HY, Lieberman JA, Kennedy JL, et al. Association study of polymorphisms in leptin and leptin receptor genes with antipsychotic-induced body weight gain. Prog Neuropsychopharmacol Biol Psychiatry. 2012;38(2):134–41.CrossRefPubMed
17.
Qin J, Shi D, Dai J, Zhu L, 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):704–6.CrossRefPubMed
18.
Ma XJ, Guo HH, Hao SW, Sun SX, Yang XC, Yu B, Jin QH. Association of single nucleotide polymorphisms (SNPs) in leptin receptor gene with knee osteoarthritis in the Ningxia Hui population. Yi Chuan. 2013;35(3):359–64.CrossRefPubMed
19.
20.
Manek NJ, Hart D, Spector TD, MacGregor AJ. The association of body mass index and osteoarthritis of the knee joint: an examination of genetic and environmental influences. Arthritis Rheum. 2003;48(4):1024–9.CrossRefPubMed
21.
Yucesoy B, Charles LE, Baker B, Burchfiel CM. Occupational and genetic risk factors for osteoarthritis: a review. Work. 2015;50(2):261–73.PubMedPubMedCentral
22.
Wang L, Guo L, Tian F, Hao R, Yang T. Analysis of single nucleotide polymorphisms within ADAM12 and risk of knee osteoarthritis in a Chinese Han population. Biomed Res Int. 2015;2015:518643.PubMedPubMedCentral
23.
Zhang R, Yao J, Xu P, Ji B, Voegeli G, Hou W, Li H, Wang Y, Kelsoe JR, Ma J. Association between genetic variants of DVWA and osteoarthritis of the knee and hip: a comprehensive meta-analysis. Int J Clin Exp Med. 2015;8(6):9430–7.PubMedPubMedCentral
24.
Tawonsawatruk T, Changthong T, Pingsuthiwong S, Trachoo O, Sura T, Wajanavisit W. A genetic association study between growth differentiation factor 5 (GDF 5) polymorphism and knee osteoarthritis in Thai population. J Orthop Surg Res. 2011;6:47.CrossRefPubMedPubMedCentral
25.
Srikanth VK, Fryer JL, Zhai G, Winzenberg TM, Hosmer D, Jones G. A meta-analysis of sex differences prevalence, incidence and severity of osteoarthritis. Osteoarthritis Cartilage. 2005;13(9):769–81.CrossRefPubMed
26.
27.
Valdes AM, Loughlin J, Oene MV, Chapman K, Surdulescu GL, Doherty M, Spector TD. Sex and ethnic differences in the association of ASPN, CALM1, COL2A1, COMP, and FRZB with genetic susceptibility to osteoarthritis of the knee. Arthritis Rheum. 2007;56(1):137–46.CrossRefPubMed
28.
Faber SC, Eckstein F, Lukasz S, Muhlbauer R, Hohe J, Englmeier KH, Reiser M. Gender differences in knee joint cartilage thickness, volume and articular surface areas: assessment with quantitative three-dimensional MR imaging. Skeletal Radiol. 2001;30(3):144–50.CrossRefPubMed
29.
Valdes AM, Hart DJ, Jones KA, Surdulescu G, Swarbrick P, Doyle DV, Schafer AJ, Spector TD. Association study of candidate genes for the prevalence and progression of knee osteoarthritis. Arthritis Rheum. 2004;50(8):2497–507.CrossRefPubMed
30.
Wu X, Kondragunta V, Kornman KS, Wang HY, Duff GW, Renner JB, Jordan JM. IL-1 receptor antagonist gene as a predictive biomarker of progression of knee osteoarthritis in a population cohort. Osteoarthritis Cartilage. 2013;21(7):930–8.CrossRefPubMedPubMedCentral
31.
Valdes AM, Hassett G, Hart DJ, Spector TD. Radiographic progression of lumbar spine disc degeneration is influenced by variation at inflammatory genes: a candidate SNP association study in the Chingford cohort. Spine (Phila Pa 1976). 2005;30(21):2445–51.CrossRef
32.
Rego-Perez I, Fernandez-Moreno M, Fernandez-Lopez C, Arenas J, Blanco FJ. Mitochondrial DNA haplogroups: role in the prevalence and severity of knee osteoarthritis. Arthritis Rheum. 2008;58(8):2387–96.CrossRefPubMed
33.
Li Y, Geng J, Wang Y, Lu Q, Du Y, Wang W, Li Z. The role of leptin receptor gene polymorphisms in determining the susceptibility and prognosis of NSCLC in Chinese patients. J Cancer Res Clin Oncol. 2012;138(2):311–6.CrossRefPubMed
34.
Mohammadzadeh G, Ghaffari MA, Bafandeh A, Hosseini SM. Effect of leptin receptor Q223R polymorphism on breast cancer risk. Iran J Basic Med Sci. 2014;17(8):588–94.PubMedPubMedCentral
35.
Rodrigues PR, Maia LL, Santos M, Peterle GT, Alves LU, Takamori JT, Souza RP, Barbosa WM, Mercante AM, Nunes FD, et al. Leptin receptor expression and Gln223Arg polymorphism as prognostic markers in oral and oropharyngeal cancer. Genet Mol Res. 2015;14(4):14979–88.CrossRefPubMed
36.
Karimi K, Arkani M, Safaei A, Pourhoseingholi MA, Mohebbi SR, Fatemi SR, Vafaei M. Association of leptin receptor gene Gln223Arg polymorphism with susceptibility to colorectal cancer. Gastroenterol Hepatol Bed Bench. 2011;4(4):192–8.PubMedPubMedCentral
37.
Gu P, Jiang W, Chen M, Lu B, Shao J, Du H, Jiang S. Association of leptin receptor gene polymorphisms and essential hypertension in a Chinese population. J Endocrinol Invest. 2012;35(9):859–65.PubMed
38.
Liu Y, Lou YQ, Liu K, Liu JL, Wang ZG, Wen J, Zhao Q, Wen SJ, Xiao L. Role of leptin receptor gene polymorphisms in susceptibility to the development of essential hypertension: a case–control association study in a Northern Han Chinese population. J Hum Hypertens. 2014;28(9):551–6.CrossRefPubMedPubMedCentral
39.
Zheng H, Xie N, Xu H, Huang J, Xie X, Luo M. Association of Gln223Arg polymorphism of the leptin receptor with hypertensive left ventricular hypertrophy. Folia Biol (Praha). 2013;59(6):246–52.
40.
Mackey-Lawrence NM, Guo X, Sturdevant DE, Virtaneva K, Hernandez MM, Houpt E, Sher A, Porcella SF, Petri Jr WA. Effect of the leptin receptor Q223R polymorphism on the host transcriptome following infection with Entamoeba histolytica. Infect Immun. 2013;81(5):1460–70.CrossRefPubMedPubMedCentral
41.
Riestra P, Garcia-Anguita A, Torres-Cantero A, Bayonas MJ, De Oya M, Garces C. Association of the Q223R polymorphism with age at menarche in the leptin receptor gene in humans. Biol Reprod. 2011;84(4):752–5.CrossRefPubMed
Metadata
Title
Association of rs1137101 polymorphism in LEPR and susceptibility to knee osteoarthritis in a Northwest Chinese Han population
Authors
Jianhui Yang
Heng Du
Jianguo Lv
Lianhe Zhang
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2016
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/s12891-016-1162-0

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