Yang Jianhui, Du Heng, Lv Jianguo, Zhang Lianhe
Rehabilitation Center, First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, No. 277, Yanta West Road, Xi'an, 710061, Shaanxi Province, People's Republic of China.
Department of Orthopedics, First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi Province, People's Republic of China.
BMC Musculoskelet Disord. 2016 Jul 25;17:311. doi: 10.1186/s12891-016-1162-0.
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.
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.
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.
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.
骨关节炎（OA）是一种复杂的关节炎病症，其中遗传因素起着关键作用。瘦素受体（LEPR）基因的单核苷酸多态性（SNP）rs1137101（Gln223Arg）已被证明与膝关节OA易感性相关。然而，中国汉族人群中的这种关联从未被研究过。本研究旨在调查Gln223Arg是否与中国西北汉族人群的膝关节OA易感性相关。
采用聚合酶链反应-限制性片段长度多态性分析对587例确诊膝关节OA患者和628例年龄和性别匹配的健康对照进行Gln223Arg多态性基因分型。此外，通过对PCR产物进行直接DNA测序分析来验证LEPR基因型。
病例组和对照组之间LEPR SNP rs1137101的基因型和等位基因频率存在显著差异（基因型：χ² = 6.52，P = 0.038；等位基因频率：χ² = 5.06，P = 0.024）。在显性遗传模型（GG + GA与AA）中，rs1137101与膝关节OA相关（P = 0.016），并且在所有膝关节OA患者和对照组中存在更高的G等位基因频率（P = 0.024）。分层分析显示，基因型GG和G等位基因与年轻（≤65岁）和老年组（>65岁）女性以及轻度膝关节OA患者的膝关节OA易感性相关。
我们的研究结果表明，LEPR基因rs1137101的基因变异与中国西北汉族人群的膝关节OA易感性独立相关，并可能作为确定膝关节OA风险的潜在生物标志物。
