The tumor necrosis factor-α -238G/A and IL-6 -572G/C gene polymorphisms and the risk of idiopathic dilated cardiomyopathy: a meta-analysis of 25 studies including 9493 cases and 13,971 controls.

Abstract

Inflammation plays an imperative role in the etiology of cardiovascular diseases (CVD). The role of cytokines in the development and progression of idiopathic dilated cardiomyopathy (IDCM) is still uncertain. The current study was conducted to evaluate the association of tumor necrosis factor-α (TNF-α) -238G/A and IL-6 -572G/C gene polymorphism with IDCM in a Pakistani population. IDCM cases (n=250) and healthy controls (n=300) were genotyped using PCR-RFLP. The variant genotypes of both the loci showed significant differences between patients and controls (p<0.05). However, -238G/A polymorphism did not show association with the disease in the presence of covariates. We also conducted a meta-analysis of both the loci with regards to CVD in accordance with the Prisma checklist. No significant relation of the TNF-α -238G/A polymorphism with CVD was found; however, this single nucleotide polymorphism (SNP) showed an association with the disease in the Asian population after subgroup analysis (p=0.01). Whereas, the IL-6 -572G/C polymorphism showed that the variant genotype (GC+CC) was associated with higher risk of CVD in contrast to the GG genotype. Furthermore, subgroup meta-analysis demonstrated a significant association of the -572 polymorphism with CVD in Asians, but no association was observed among Western populations with this SNP. Our findings support an association between the IL-6 -572G/C polymorphism and IDCM risk. The role of the TNF-α -238G/A polymorphism in IDCM is still unclear. Further studies are warranted to determine the serum cytokine levels in relation to the cytokines' SNP in diverse ethnic groups to ascertain the molecular basis of the disease pathology.