Hämäläinen S, Solovieva S, Vehmas T, Hirvonen A, Leino-Arjas P
a Finnish Institute of Occupational Health , Helsinki , Finland.
b Clinicum , University of Helsinki , Helsinki , Finland.
Scand J Rheumatol. 2018 Jan;47(1):71-78. doi: 10.1080/03009742.2017.1314000. Epub 2017 Aug 16.
Available evidence suggests that genetic factors and overweight play major roles in the aetiology of osteoarthritis (OA). We analysed the association of 18 single-nucleotide polymorphisms (SNPs) from nine adipokine and adipokine receptor genes (LEP, LEPR, ADIPOQ, RETN, NAMPT, SERPINA12, ITLN1, RARRES2, and APLN) with radiographic hand OA.
The study design was cross-sectional. Bilateral hand radiographs of 542 occupationally active Finnish female dentists and teachers aged 45-63 years were examined and classified for the presence of hand OA using reference images. Hand OA was defined as at least three finger joints with radiographic OA of grade 2-4. The genotypes were determined using polymerase chain reaction-based methods. Body mass index (BMI) was calculated based on self-reported height and measured weight. Associations of the individual SNPs and their haplotypes with hand OA were tested using logistic regression analysis.
The minor allele of RETN rs10401670 was associated with a decreased [odds ratio (OR) = 0.73, 95% confidence interval (CI) 0.55-0.97, p = 0.03] and RARRES2 rs4721 with an increased (OR 1.41, 95% CI 1.07-1.87, p = 0.01) prevalence of hand OA. Also, LEPR AC (OR 1.54, 95% CI 1.01-2.35, p = 0.05) and RETN GGTT (OR 0.58, 95% CI 0.37-0.93, p = 0.02) haplotypes were associated with hand OA. These associations were modified by BMI when comparing normal and overweight women. However, the associations lost their statistical significance after adjusting for multiple testing.
Our results suggest weak associations between the studied variations in LEPR, RARRES2, and RETN genes and hand OA in Finnish women, and that the associations are modified by BMI. However, these associations could not be verified in the current study.
现有证据表明,遗传因素和超重在骨关节炎(OA)的病因中起主要作用。我们分析了来自9个脂肪因子和脂肪因子受体基因(LEP、LEPR、ADIPOQ、RETN、NAMPT、SERPINA12、ITLN1、RARRES2和APLN)的18个单核苷酸多态性(SNP)与手部放射学OA的关联。
本研究设计为横断面研究。对542名年龄在45 - 63岁、职业活跃的芬兰女牙医和女教师的双侧手部X光片进行检查,并使用参考图像对手部OA的存在情况进行分类。手部OA定义为至少三个指关节有2 - 4级放射学OA。使用基于聚合酶链反应的方法确定基因型。根据自我报告的身高和测量的体重计算体重指数(BMI)。使用逻辑回归分析测试各个SNP及其单倍型与手部OA的关联。
RETN rs10401670的次要等位基因与手部OA患病率降低相关[比值比(OR)= 0.73,95%置信区间(CI)0.55 - 0.97,p = 0.03],而RARRES2 rs4721与患病率升高相关(OR 1.41,95% CI 1.07 - 1.87,p = 0.01)。此外,LEPR AC(OR 1.54,95% CI 1.01 - 2.35,p = 0.05)和RETN GGTT(OR 0.58,95% CI 0.37 - 0.93,p = 0.02)单倍型与手部OA相关。在比较正常体重和超重女性时,这些关联受到BMI的影响。然而,在进行多重检验校正后,这些关联失去了统计学意义。
我们的结果表明,芬兰女性中LEPR、RARRESs2和RETN基因的研究变异与手部OA之间存在弱关联,并且这些关联受到BMI的影响。然而,这些关联在当前研究中无法得到验证。