Abstract
The aim of the present study is to investigate the functional role of TNF-α single-nucleotide polymorphisms/haplotypes in an association with reproductive tract infections (RTIs) in symptomatic and asymptomatic women. A total of 850 consecutive subjects consisting of 400 cases and 450 healthy controls, were screened for RTIs, along with their risk factors and associated symptoms. The propensity score matching was performed to reduce the confounding bias arise owing to covariates and to balance the data between two groups. A total of 211 pairs (1:1) have been created. Genotyping of rs1800629 (-308) and rs361525 (-238) SNPs of TNF-α was done by PCR–RFLP followed by sequencing. The functional implication of TNF-α SNPs in an association with RTIs was also checked by using ELISA. The frequency of -238A allele and -308A allele was found to be twofold (P < 0.0001) and threefold (P < 0.0001) higher in the presence of RTIs. AA haplotype emerged as a major player in an association with RTIs and elevated TNF-α expression. The present study revealed the functional role of rs1800629 (-308) and rs361525 (-238) of TNF-α in an association with RTIs. This information may be used to establish biomarkers for an inflammatory response during the persistence of RTIs.
Highlights
The aim of the present study is to investigate the functional role of TNF-α single-nucleotide polymorphisms/haplotypes in an association with reproductive tract infections (RTIs) in symptomatic and asymptomatic women
The predictable odds ratio (OR) of infection was found to be at 5.6 fold (OR = 5.686, 95% confidence intervals (CIs) 3.290–9.826; P = 0.0001) AOR = 4.560, 95% CI 2.427–8.565) higher in cases as compared to controls
The present study revealed the potential role of genetic variations in immunomodulatory TNF-α -308 G/A and -238 G/A single-nucleotide polymorphisms (SNPs), associated with reproductive tract infections in Indian population
Summary
The aim of the present study is to investigate the functional role of TNF-α single-nucleotide polymorphisms/haplotypes in an association with reproductive tract infections (RTIs) in symptomatic and asymptomatic women. Increased burden of RTIs due to most infections are asymptomatic and remain untreated RTIs. As per published epidemiological data, among pregnant women in developing countries, it is estimated that gonorrhea rates are 10–15 times higher, Chlamydia rates are 2–3 times higher, and Syphilis rates are 10–100 times higher than the rates of STDs among women in industrialized countries[4]. TNF-α is a proinflammatory cytokine, it plays an important role in many inflammatory diseases[7] It is located on chromosome 6p21.231 in the polymorphic region of MHC-III. The TNF-α has been associated with various cancers, such as Oral cancer[12], breast carcinoma[13], most important cervical cancer[9,14] and renal cell carcinoma[11]
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