Endocrine Abstracts (2018) 56 P528 | DOI: 10.1530/endoabs.56.P528

Genotype- Phenotype correlations of TNF-[alpha], IL-6 and Leptin receptor gene polymorphisms in Poly cystic ovarian syndrome

Rajesh B1, Ramesh B1, Gayathri G1, Venkateshwara Reddy M1, Vighnesh D1, Rajkiran Reddy B2, Chakrapani B3 & Bhargav PRK4


1VMC, Kurnool, India; 2SMART Sunshine Hospital, Hyderabad, India; 3Neuro Hospital, Nizamabad, India; 4Endocare Hospital, vijayawada, India.


Introduction: Tumor necrosis factor alpha (TNF-α) and Interleukin-6 (IL-6) are potent immunomodulators and proinflammatory cytokines displaying varied functions. Apart from monocytes/macrophages, they are also produced by the cells in female reproductive tract. Polycystic ovarian syndrome (PCOS) is one of the commonest endocrine disorder amongst women of reproductive age group. Several polymorphisms in the promoter region of the gene TNF-α, IL-6 and Leptin receptors have been described associated with various disease ranging from cancers to PCOS, obesity and infertility. In this context, we evaluated association between PCOS and the promoter single nucleotide polymorphisms of the gene TNF-α –238G/A (rs361525), –308G/A (rs1800629) and –1031T/C (rs1799964); IL-6 –174G/C and LEPR 668 A/G.

Material and methods: This is inter-disciplinary study conducted by collaboration between a tertiary care endocrinology hospital, biochemistry department of a teaching medical institute and genetics lab. In this prospective study involving 100 PCOS patients with 100 age matched controls, we employed 3 sets of primers and screened for the known single nucleotide polymorphisms TNF-α, IL-6 and Leptin receptor genes. Apart from qualitative and quantitative evaluation, linkage disequilibrium, multifactor dimensionality reduction analysis and In-silico analysis were performed.

Results: Of identified seventeen haplotypes the haplotype combination “A-A-C-A-C” and “A-G-T-G-C” conferred protection towards PCOS (OR=0.321, CI=0.15 – 0.67, P=0.002 and OR=0.28, CI=0.11 – 0.73, P=0.005 respectively), while the haplotype combination “A-G-C-A-C” conferred fourfold risk (OR=3.38, CI=1.52 – 7.53, P=0.0018) towards PCOS susceptibility. For IL-6 - 174G/C, the percentage of GG, GA and AA genotypes in patients was 24, 44, 32 while it was 25, 45 and 30 in controls respectively. For LEPR gene, the relative risk for the alleles demonstrated a twofold risk of G allele towards disease establishment (OR=1.62, CI=1.07 – 2.45, P=0.021).

Conclusions: The present study could not provide a concrete association between the TNF α and IL-6 polymorphisms with PCOS. For Leptin receptor gene, there appears to be role of the AG and GG genotypes, and G allele in contributing towards establishment and progression of PCOS. But further extensive studies are warranted to validate the same phenomenon in the general population and various ethnic groups.

(Key words: PCOS; Rotterdam criteria; Pol;ymorphisms; TNF-alpha; IL-6; Leptin receptor gene; Cytokines; Infertility)

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