GDF5 和 ADAM12 基因与膝骨关节炎的关联分析。

Genetic association analysis of GDF5 and ADAM12 for knee osteoarthritis.

机构信息

Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.

出版信息

Joint Bone Spine. 2012 Oct;79(5):488-91. doi: 10.1016/j.jbspin.2011.10.016. Epub 2012 Jan 28.

DOI:10.1016/j.jbspin.2011.10.016

PMID:22284607

Abstract

OBJECTIVES

To examine two single-nucleotide polymorphisms (SNPs) for their association with knee osteoarthritis (OA) susceptibility in Korean cohort.

METHODS

Two thousand four hundred and sixty-two subjects aged 50 years and older were assessed for OA at the knee, were genotyped with two SNPs (GDF5; rs143383 and ADAM12; rs3740199). Radiographs were read by two examiners that used an atlas of radiographic features to obtain a global Kellgren/Lawrence (K/L) score. Genomic DNA was extracted from peripheral blood using a QIAamp DNA Blood Mini Kit. GDF5 genotyping was performed by high resolution melting analysis. ADAM12 genotyping was performed by TaqMan assay. The allele frequencies were assessed by counting alleles. Associations were tested by calculating the odds ratios (ORs) and 95% confidence intervals (95% CIs), using logistic regression analysis with adjustments for age, gender and body mass index (BMI).

RESULTS

Of this cohort, 725 subjects had radiographic OA (defined as a K/L score of ≥ 2). The mean age of the OA patients (females: 76.4%) was 67.4 (7.9) years. In GDF5, we observed a T-allele frequency of 74.1% in our controls, compared with that of 73.7% in patients (P = 0.72; OR 0.97, 95% CI; 0.83-1.13). In ADAM12, the frequency of G-allele in the case (54.6%) versus the control (55.0%) was calculated (P = 0.94, OR 1.01, 95% CI; 0.88-1.15). There was no significant difference in the genotype frequencies between the patients and healthy controls.

CONCLUSION

The associations of two SNPs with OA that were noted in previous studies, were not found in the Korean OA cohort.

摘要

目的

在韩国队列中，研究两个单核苷酸多态性（SNPs）与膝骨关节炎（OA）易感性的关系。

方法

对 2462 名年龄在 50 岁及以上的受试者进行膝关节 OA 评估，对两个 SNPs（GDF5；rs143383 和 ADAM12；rs3740199）进行基因分型。使用放射学特征图谱由两名阅片者读取放射照片，获得全局 Kellgren/Lawrence（K/L）评分。使用 QIAamp DNA 血液迷你试剂盒从外周血中提取基因组 DNA。通过高分辨率熔解分析进行 GDF5 基因分型。通过 TaqMan 测定进行 ADAM12 基因分型。通过计数等位基因评估等位基因频率。使用 logistic 回归分析，通过调整年龄、性别和体重指数（BMI），计算比值比（ORs）和 95%置信区间（95%CI），检验关联。

结果

在该队列中，725 名受试者有放射学 OA（定义为 K/L 评分≥2）。OA 患者（女性：76.4%）的平均年龄为 67.4（7.9）岁。在 GDF5 中，我们观察到对照组的 T 等位基因频率为 74.1%，而患者为 73.7%（P=0.72；OR 0.97，95%CI；0.83-1.13）。在 ADAM12 中，病例（54.6%）与对照（55.0%）中 G 等位基因的频率进行了计算（P=0.94，OR 1.01，95%CI；0.88-1.15）。患者与健康对照组之间的基因型频率无显著差异。