Genetic association analysis of GDF5 and ADAM12 for knee osteoarthritis

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.