Family association study between tumour necrosis factor a gene polymorphisms and polycystic ovary syndrome in Han Chinese

Abstract

Polycystic ovary syndrome (PCOS) is a complex disease involving genetic and environmental components. Tumour necrosis factor a (TNFa) is a proinflammatory cytokine in the pathogenesis of PCOS. The genetic association between polymorphisms of TNFa gene and PCOS was investigated. A family based study was conducted with 216 family trios (648 participants) having a proband with PCOS. Transmission disequilibrium test (TDT) was used to analyse the association between two single nucleotide polymorphisms (SNP) (rs1799964, rs1799724) of TNFa gene and PCOS. Minor allele frequencies of the SNP were 0.178 (rs1799964) and 0.118 (rs1799724). The two SNP were in Hardy-Weinberg equilibrium; TDT was only conducted when one parent was heterozygous. Of 216 trios, 112 trios of rs1799964 and 76 trios of rs1799724 were tested. A significant difference in transmission was found for rs1799964 (transmitted: non-transmitted = 73 : 39; χ(2) = 10.321; P = 0.0013). rs1799724 showed no evidence of an association with PCOS; risk alleles were over transmitted (transmitted: non-transmitted = 43 : 33; χ(2) = 1.316). Transmission disequilibrium of the two SNP indicated that rs1799964 may participate in the pathogenesis of PCOS in Chinese women. These data provide a basis for further studies of TNFa in the cause of PCOS.

Preliminary study showing no association between G238A (rs361525) tumor necrosis factor-α (TNF-α) gene polymorphism and its serum level, hormonal and biochemical aspects of polycystic ovary syndrome

“…Recent investigations have shown that rs1799964 polymorphism in the promoter region of the TNF-α gene could be associated with PCOS [ 1 , 3 , 16 ]. In contrast, several studies have revealed a lack of direct involvement of rs1800629 polymorphism of the TNF-α gene in PCOS patients in South Indian, Turkish, and Australian populations [ 2 , 3 , 15 ].…”

“…Polycystic ovary syndrome (PCOS) is a major cause of female infertility, affecting 6–10% of women during reproductive age; moreover, it is one of the most prevalent endocrine disorders [ 1 ]. This syndrome is associated with increased risks of obesity, type 2 diabetes mellitus, hyperinsulinemia, insulin resistance, cardiovascular disease, and dyslipidemia [ 1 , 2 ].…”

“…Polycystic ovary syndrome (PCOS) is a major cause of female infertility, affecting 6–10% of women during reproductive age; moreover, it is one of the most prevalent endocrine disorders [ 1 ]. This syndrome is associated with increased risks of obesity, type 2 diabetes mellitus, hyperinsulinemia, insulin resistance, cardiovascular disease, and dyslipidemia [ 1 , 2 ]. Evidence indicates an interaction among genetic, biochemical, environmental, and immunological factors in the pathogenesis of PCOS [ 2 , 3 ] .Among the immunological factors, a disequilibrium of pro−/anti-inflammatory cytokines has been offered as a key contributor [ 2 ].…”

“…Therefore, different concentrations of serum TNF-α can be produced, leading to many sorts of disorders [ 3 , 15 ]. Studies in Chinese, Korean, and South Indian populations have revealed a relationship between polymorphisms in the promoter region of the TNF-α gene and PCOS [ 1 , 3 , 16 ], hyperandrogenism [ 9 ], type 2 diabetes [ 17 ], and obesity [ 18 ].…”

Single nucleotide polymorphisms in the TGF-β1 gene are associated with polycystic ovary syndrome susceptibility and characteristics: a study in Korean women

“…Moreover, inheritance patterns, characterized by complex polygenic traits, further complicate the identification of genetic factors. Genetic susceptibility studies of PCOS have focused on genes related to the metabolism of adipose tissue and steroid hormones and the release and action of gonadotropin and insulin and inflammatory cytokine genes [3][4][5][6][7][8]. However, it is difficult to establish which genes are involved due to a wide range Capsule This study demonstrates that TGF-β1 gene SNPs are associated with PCOS development (rs1800469 and rs4803457) and with PCOS characteristics in Korean women (rs1800469 and rs2317130), as assessed by laboratory and clinical measurements.…”