No association between the 308 polymorphism in the tumour necrosis factor alpha (TNFalpha) promoter region and polycystic ovaries

Abstract

The tumour necrosis factor (TNF)2 allele appears to be linked with increased insulin resistance and obesity, conditions often found in overweight patients with polycystic ovary syndrome (PCOS). The significance of TNFalpha polymorphism in relation to the clinical and biochemical parameters associated with PCOS was investigated in 122 well-characterized patients with polycystic ovaries (PCO). Of these, 84 had an abnormal menstrual cycle and were classified as having PCOS, while the remaining 38 had a normal menstrual cycle and were classified as having PCO. There were a further 28 individuals without PCO (non-PCO) and 108 individuals whose PCO status was undetermined (reference population). The promoter region of the TNFalpha gene was amplified by polymerase chain reaction (PCR), and the presence or absence of the polymorphism at -308 was determined by single-strand conformational polymorphism (SSCP) analysis. The less common TNF allele (TNF2) was found as TNF1/2 or TNF2/2 in 11/38 (29%) of PCO subjects, 25/84 (30%) of PCOS subjects, 7/28 (25%) of non-PCO subjects, and 45/108 (42%) of the reference population. There was no significant difference in the incidence of the TNF2 allele between the groups. The relationship of TNF genotype to clinical and biochemical parameters was examined. In both the PCO group and the PCOS group, the presence of the TNF2 allele was significantly associated with lower glucose values obtained from the glucose tolerance testing (P<0.05). The TNF genotype was not significantly associated with any clinical or biochemical parameter measured in the PCO, PCOS or non-PCOS groups. Thus, the TNFalpha -308 polymorphism does not appear to strongly influence genetic susceptibility to polycystic ovaries.

Associations between TNF-α and interleukin gene polymorphisms with polycystic ovary syndrome risk: a systematic review and meta-analysis

“…For -308G>A, 582 PCOS cases and 563 controls from 4 articles [32,31,17,27] were included. For -805C>T, 87 cases and 115 controls were analyzed from the study by Korhonen [29].…”

TNF-α haplotype association with polycystic ovary syndrome – a South Indian study

“…Several polymorphisms in the promoter region have been associated with conditions such as insulin resistance, obesity, pre-eclampsia, endometriosis including PCOS [4,12,13]. More recent studies have provided evidence for a role of TNF-α in obesity and insulin resistance, indicating that perturbations of TNF-α metabolism may affect the onset of non-insulin-dependent diabetes mellitus (NIDDM) and may play a role in the development of cardiovascular disorders [8]; the conditions often considered as long term complications of PCOS (Table 1; [14][15][16][17][18][19][20][21][22]). …”

Inter-Ethnic Variations in Association of TNF-Alpha G308a Single Nucleotide Polymorphism with Type 2 Diabetes Mellitus - A Review

“…There was also strong negative association between 308 A allele and S. HDL-cholesterol, although insulin resistance was positively associated with BMI and waist circumference (WC) in all obese irrespective of G or A allele in obese Australians [45]. No significant differences by polymorphism carrier status were found for insulin resistance in Australian females [46], in diabetic Japanese patients [29,47], in Danish Caucasians [30], in obese Americans [48], in young healthy relatives of type 2 diabetic German Caucasians [49], in Hong Kong Chinese [50], in obese and lean Romans [51] and in overweight IGT Finnish subjects [20]. This association was neither found in relatives of type 2 diabetic British Caucasians and in controls [52] …”

“…16 TNF-α allele was found to be associated with higher BMI, waist and hip circumference and total body fat in obese Spanish Caucasians [57]. However, 308A allele was not associated with obesity in Australian females [46], in diabetic and non-diabetic subjects from New England [21], in obese Caucasians and African Americans [48], in diabetic Japanese [58], in obese Chinese [39], in elderly Chilean women [59], in healthy Tunisians [60], in obese and lean Romans [51] and in obese Australians [31]. TNF-α -308A allele did not affect the amount of weight loss in male and female Danish Caucasians in another study [30].…”

“…There was also strong negative association between 308 A allele and S. HDL-cholesterol, although insulin resistance was positively associated with BMI and waist circumference (WC) in all obese irrespective of G or A allele in obese Australians [45]. No significant differences by polymorphism carrier status were found for insulin resistance in Australian females [46], in diabetic Japanese patients [29,47] …”