Susceptibility Risk Alleles of -238G/A, -308G/A and -1031T/C Promoter Polymorphisms of TNF-α Gene to Uterine Leiomyomas.

BACKGROUND

Uterine Leiomyomas (UL) are non-cancerous single celled mass of uterine smooth muscles distinguished by presence of large amounts of collagen, fibronectin and proteoglycans. Tumor necrosis factor-α (TNF-α), an inflammation inducing cytokine, plays a major role in various disorders of the immune system; is involved in tumor development and progression. It is proposed to study the influence of three functional promoter polymorphisms of TNF-α viz -238G/A, -308G/A and -1031T/C in the development and progression of UL.

METHODOLOGY: Study included 146 individuals positive for uterine fibroids and 150 healthy individuals. Genomic DNA was isolated from white blood corpuscles and subjected to PCR-RFLP analysis and Allele Specific PCR (ARMS). The significance of the obtained data in controls and patients was estimated and computed by adopting appropriate statistical tools.

RESULTS

In this study an association between TNF-α -1031T/C polymorphism and UL was reported. A significant association of the TC genotype (χ(2) - 14.34; p=0.0008) and the C allele (χ(2) - 5.898 p=0.015) with uterine leiomyomas was observed. Likewise odds risk estimates of 2.56 (95% CI 1.56-4.20, p=0.0007) revealed a significant association of TC genotype and C allele with uterine leiomyomas.

CONCLUSIONS

"TC" genotype and "C" allele of rs1799964 (-1031T/C) is associated with higher risks to leiomyomas. The "C" allele of -1031T/C results in an increased expression TNF-α leading to smooth cell proliferation and tumor progression, hence, may be a relevant molecular marker in the identification and establishment of UL.