The Study Of Polymorphisms Of FTO,TNF-?and FSHR Genes And Susceptibility To Polycystic Ovary Syndrome

Objective: To explore the associations between five polymorphisms of FTO, TNF-? and FSHR genes and susceptibility to polycystic ovary syndrome as well as its clinical and/or biochemical characteristics.Methods: A total of 102 PCOS females were randomly recruited into current study at reproductive health hospital of Nanhua-Xinghui from October 2014 to August 2015. The diagnostic criteria of PCOS was based on the criteria of Rotterdam Revised 2003 recommended by academic conference of European society of human reproduction and embryology and the American society for reproductive medicine. Meanwhile, 96 women receiving in vitro fertilisation(IVF) because of infertility caused by male factors were served as control group and all of them had no history of menstrual disorders, diabetes, high blood pressure, endocrine disorder and other related diseases. For every subject, 2 ml elbow vein blood was collected between the 2nd and 4th days of the menstrual cycle,or any day if the patient was amenorrheheic, then was mixed with EDTA-Na. A volume of 600 ?l anticoagulant vein blood was used to extract whole blood genome DNA and the method of immune chemiluminescence(Beckman) was appiled to detect the level of follicle-stimulating hormone(FSH), luteinizing hormone(LH), estradiol(E2), testosterone(T), prolactin(PRL), progesterone(P) of the rest blood.On-off switch mediated by high-fidelity DNA polymerase was used to test genotype of following SNPs: FTO rs9939609A/T, FTO rs9926289A/G, TNF-?-238A/G, TNF-?-857C/T. Meanwhile, FSHR-29A/G was genotype by PCR-RFLP. Furthermore, The frequency of genotype and allele were calculated, and the difference of frequency distribution between PCOS women and control group was analyzed. Finally, we analyzed the relationship of these SNPs and susceptibility to polycystic ovary syndrome as well as its clinical and/or biochemical characteristics.Results:1. For rs9939609 A/T, the frequencies of TT, AT and AA genotype was 77.5 %, 21.5 %, 1.0 % in PCOS group and 77.1 %, 12.5 %, 10.4 % in control group with significant difference(P=0.006). However, no significant relationships were found under other genetic models(For TT and AT+AA : 77.1 %, 22.9 % in control, 77.5 %, 22.5 % in PCOS,P=0.951; For T and A: 88.2 %, 11.8 % in PCOS, 83.3 %, 16.7 % in control, P=0.162). Compared with TT genotype, AT+AA genotype showed no statistic difference in clinical and/or biochemical data.2. For rs9926289 A/G, the frequencies of GG, AG and AA genotype were 85.9 %, 10.9 %, 3.2 % in PCOS group and 92.2 %, 5.6 %, 2.2 % in control group without significant difference(P=0.378). No significant relationships were found under other genetic models(For GG and AG+AA : 92.2 %, 7.8 % in control, 85.9 %, 14.1 % in PCOS, P=0.171;For G and A: 91.3 %, 8.7 % in PCOS, 95.0 %, 5.0 % in control, P=0.163).However, in PCOS group, the level of progesterone showed significant difference between patients with GG genotype and A allele carriers.3. For TNF-?-857 C/T, the frequencies of CC, CT and TT genotype were 31.4 %, 60.8 %, 7.8 % in PCOS group and 51.0 %, 44.8 %, 4.2 % in control group with significant difference(P=0.017). The frequencies of C and T allele were 61.8 %, 38.2 % in PCOS and 73.4 %, 26.6 % in controlwith significant difference(P=0.013). In PCOS group, both the level of LH(m Iu/ml) and Glucose in CC, CT and TT individuals showed significant difference(P=0.037, P=0.003) and these significance differences were presented in CC subjects and T allele carriers(P=0.012?P=0.001?4. For TNF-?-238 A/G, AA genotype was not founded in current samples. The frequencies of GG and AG genotype were 97.1 %, 2.9 % in PCOS group and 96.9 %, 3.1 %, in control group without significant difference(P=1.000). The frequencies of G and A allele were 98.5 %,1.5 % in PCOS and 98.4 %, 1.6 % in control without significant difference(P=1.000).5. For FSHR-29 A/G, the frequencies of AA, AG and GG genotype were 22.5 %, 58.8 %, 18.6 % in PCOS group and 22.9%, 52.1 %, 25.0 %in control group without significant(P=0.550). In PCOS group, the level of hormone were compared among AA, AG and GG group without significant difference.Conclusions:1. Our results suggested that FTO rs9939609A/T and TNF-?-857C/T are associated with susceptibility to PCOS.2. FTO rs9939609A/T is associated with progesterone in PCOS women.3. TNF-?-857 C/T were related with both LH and Glucose in PCOS subjects.