Interleukin-6 (-572) and Tumor Necrosis Factor α (-308 and-238) Polymorphisms and Risk of Knee Osteoarthritis in a Pakistani Population: A Case-Control Study

Osteoarthritis (OA) is one of the most common musculoskeletal diseases of adults worldwide. Inflammation plays a crucial part in OA pathology, but role of cytokines is still inconclusive. Purpose of this study was to assess the function of tumor necrosis factor alpha (TNF-alpha -308 and -238) and interleukin-6 (IL6-572) polymorphisms in OA disease susceptibility in a Pakistani population. 280 OA patients and 308 ethnically matched healthy controls were enrolled in the current study. Demographic data were collected from all participants via a questionnaire. Genomic DNA was isolated from all subjects. TNF-alpha (-308 G>A, -238 G>A) and IL6 (-572 G>C) polymorphisms in both groups were identified by PCR-coupled restriction fragment length polymorphism (PCR-RFLP) technique. GraphPad Prism software was used to perform statistical analysis. Genotypic and allelic frequencies were determined in both groups. Basic characteristics were mentioned as SD +/- mean. p value above 0.05 was considered nonsignificant statistically. Age and body mass index (BMI) differences were not significant (>0.05) between patients and control groups. Genotype frequencies were in agreement with Hardy-Weinberg equilibrium for all single nucleotide polymorphisms (SNPs) in control and patient group. TNF-alpha (-308, -238) GA+AA genotypes and IL6 (-572) GC+CC genotypes were considerably associated with higher risk of OA compared to homozygous wild-type genotypes (p<0.01). Variant alleles were more expressed in knee OA patients as compared to healthy controls for all loci (p<0.05). Our finding suggests there is an association between TNF-alpha -308G/A, -238G/A and IL6-572G/C polymorphisms and OA disease susceptibility in a Pakistani population. Further studies with large sample size and in diverse ethnic groups are vital to evaluate and confirm the function of these SNPs in OA disease pathology.