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Tumor necrosis factor-alpha and polycystic ovarian syndrome: a clinical, biochemical, and molecular genetic study.

ABSTRACT: Tumor necrosis factor-alpha (TNF-?) appears to be linked with hyperandrogenism (HA), increased insulin resistance (IR), and obesity (Ob), which were common features noted with polycystic ovarian syndrome (PCOS). Our aim was to study the role of TNF-? in the pathogenesis of IR and Ob in PCOS, as well as a C850T (rs1799724) polymorphism in the promoter region of the TNF-? gene, in a group of 204 PCOS patients and 204 age-matched healthy controls.Significant differences were observed between PCOS patients and controls. All the PCOS had elevated body mass index, waist circumference, waist-to-hip ratio, fasting insulin, homeostatic model assessment (HOMA) score, and serum TNF-? when compared with controls (p<0.05). Genotype distribution for the C-850T polymorphism was observed with the frequency of the variant T allele being 0% in the PCOS group and 9% in the control group (p=0.0032).In conclusion, our present results suggest that the TNF-? system might contribute to the pathogenesis of HA, Ob, and IR in PCOS independent of a polymorphism of the TNF-? C850T (rs1799724) in our population.

SUBMITTER: Thathapudi S

PROVIDER: S-EPMC4150372 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Tumor necrosis factor-alpha and polycystic ovarian syndrome: a clinical, biochemical, and molecular genetic study.

Thathapudi Sujatha S Kodati Vijayalakshmi V Erukkambattu Jayashankar J Katragadda Anuradha A Addepally Uma U Hasan Qurratulain Q

Genetic testing and molecular biomarkers 20140801 9

<h4>Background</h4>Tumor necrosis factor-alpha (TNF-α) appears to be linked with hyperandrogenism (HA), increased insulin resistance (IR), and obesity (Ob), which were common features noted with polycystic ovarian syndrome (PCOS). Our aim was to study the role of TNF-α in the pathogenesis of IR and Ob in PCOS, as well as a C850T (rs1799724) polymorphism in the promoter region of the TNF-α gene, in a group of 204 PCOS patients and 204 age-matched healthy controls.<h4>Results</h4>Significant diffe ...[more]

PMID: 25083576

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Project description:BackgroundGuillain-Barré Syndrome (GBS) is an acute acquired autoimmune inflammatory disorder of peripheral nerves and roots. The pathogenesis is essentially an aberrant post-infectious immune response in a genetically susceptible host milieu. Single nucleotide polymorphisms (SNP) in genes encoding the inflammatory mediators like TNF-α, CD1A and CD1E can influence their expression and level and the susceptibility and clinical course of disease in GBS.ObjectiveWe tried to study the susceptibility of single nucleotide polymorphisms of TNF-α and CD1 genes in Guillain-Barré Syndrome in Indian population and determine the association in terms of genotype, allele and haplotype distribution along with individual subtype, severity and clinical outcome.MethodologyIn this case-control study, we investigated the single nucleotide polymorphism pattern in the promoter region of TNF-α (-308 G/A), TNF-α (-863C/A), CD1A and CD1E genes using real-time polymerase chain reaction in 75 GBS patients and analysed in comparison with 75 age and sex-matched healthy controls.ResultsThe findings revealed that the allelic distribution of TNF-α (-308 G/A) *A allele was associated with GBS (P value 0.04, Odds Ratio 2.03, 95% Confidence Interval 1.01-4.07). There was no association found with genotype, haplotype combination and other allele distribution for GBS in the study. CD1A and CD1E SNPs did not reveal any susceptibility for GBS. The subtype analysis did not reveal any statistical significance, except for CD1A *G allele with AMAN subtype (P value 0.026). The haplotypic combinations and mutant allele of TNF-α (-308 G/A), TNF-α (-863C/A), CD1A and CD1E were significantly associated with severe GBS in the study. However, there was no association of any SNP for mortality and survival of GBS in the study.ConclusionTNF-α (-308 G/A)*A allele might confer genetic susceptibility for GBS in Indian population. CD1 genetic polymorphism could not be considered for susceptibility to GBS. TNF-α and CD1 genetic polymorphism did not affect mortality in GBS.

Project description:BACKGROUND:Polycystic ovary syndrome (PCOS) is the main cause of female infertility. Interactions among genetic, biochemical, and immunological factors can affect the pathogenesis of PCOS. As a proinflammatory cytokine, tumor necrosis factor-? (TNF-?) plays an important role in this regard. The present study aimed to evaluate the association of the rs361525 gene single-nucleotide polymorphism (SNP) and TNF-? serum levels with the hormonal and biochemical characteristics of PCOS in Iranian individuals. METHODS:The SNP rs361525 in the TNF-? gene was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in a total of 111 PCOS patients and 105 healthy females. Serum levels of TNF-?, lipid and hormone profiles, and biochemical factors were measured using enzyme-linked immunosorbent assay (ELISA) and calorimetric methods, as appropriate. RESULTS:The TNF-? serum level was higher in women with PCOS compared with the control group (p?<? 0.0001), and it was significantly correlated with the homeostasis model assessment (HOMA) factor (r?=?0.138, p?<? 0.05). No significant differences were found in the genotype and allelic frequencies between the two groups (p?>? 0.05). Higher levels and significant differences were found for the HOMA factor, luteinizing hormone/follicle-stimulating hormone (LH/FSH), testosterone, and body mass index (BMI) in the PCOS group compared with the control group (p?<? 0.0001). High LH/FSH ratios (odds ratio [OR]?=?1.98, 95% confidence interval [CI]?=?1.20-3.28, p?<? 0.01), and high HOMA factor (OR?=?5.04, 95% CI?=?2.82-9.01, p?<? 0.001) were significantly associated with an increased risk of PCOS. CONCLUSIONS:Despite the lack of significant difference between rs361525 polymorphism of the TNF-? gene and PCOS, the serum level of TNF-? was increased in PCOS patients and positively correlated with the HOMA factor. Elevation of the LH/FSH ratio and HOMA for insulin resistance (HOMA-IR) increased the risk of PCOS. Therefore, TNF-? could indirectly contribute to PCOS progression.

Dataset Information

Tumor necrosis factor-alpha and polycystic ovarian syndrome: a clinical, biochemical, and molecular genetic study.

Publications

Tumor necrosis factor-alpha and polycystic ovarian syndrome: a clinical, biochemical, and molecular genetic study.

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