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

Poly cystic ovary syndrome is the major cause of anovulatory infertility. TNF alpha, pro-inflammatory cytokine is associated with obesity, insulin resistance and hyperandrogenism, therefore in present study we tried to find the association between TNF alpha promoter polymorphisms, TNF alpha levels and the risk of PCOS. Present case control study was carried on 400 women of age 16-40 years. TNF alpha levels were measured by ELISA whereas promoter polymorphisms were evaluated by PCR-RFLP. Haplotype and Linkage disequilibrium analysis was also done. TNF alpha 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 alpha level. rs361525 and rsl 799964 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 alpha levels in PCOS and Control group suggest its 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.