Evaluating the association of TNF α promoter haplotype with its serum levels and the risk of PCOS: A case control study

•TNF α levels were measured in different PCOS phenotypes and control.•Association of TNF α levels with different promoter polymorphisms is checked.•Haplotype analysis predicted most susceptible genotype having increased TNF α levels.•Most susceptible genotype for PCOS risk was also predicted by Haplotype analysis. Poly cystic ovary syndrome is the major cause of anovulatory infertility. TNF α, pro-inflammatory cytokine is associated with obesity, insulin resistance and hyperandrogenism, therefore in present study we tried to find the association between TNF α promoter polymorphisms, TNF α levels and the risk of PCOS. Present case control study was carried on 400 women of age 16–40 years. TNF α levels were measured by ELISA whereas promoter polymorphisms were evaluated by PCR-RFLP. Haplotype and Linkage disequilibrium analysis was also done. TNF α level was significantly higher in PCOS group (13.24 ± 9.78) than control (5.5 ± 3.8). Haplotype analysis revealed that GGTCT, AGTCT, AGCCT and AACCT are the susceptible haplotypes associated with TNF α level. rs361525 and rs1799964 were found to be associated with the risk of PCOS (p = 0.0006, 0.015). GGCCT, AATAT, GATAT (most susceptible), AGCCT, GGTCT and GATCT are the susceptible haplotypes for PCOS. Significant difference between TNF α levels in PCOS and Control group suggest it's one of the promising candidates for the marker of inflammation (sensitivity and specificity 91.23 and 94.56% respectively, with area under the curve 0.907 at 95% CI 0.8723–0.9512). Presence of GGCCT haplotype suggests the susceptibility towards PCOS which needs to be further verified. In addition to this, present study not only provides a pavement for the diagnosis, but also monitoring and management of PCOS too.