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

Abstract

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 α (TNF-α -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-α (-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-α (-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-α -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.