Hum. Reprod. Advance Access published online on February 12, 2008
Human Reproduction, doi:10.1093/humrep/den016
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Association of tumor necrosis factor-
gene polymorphisms with advanced stage endometriosis
1 Department of Obstetrics and Gynecology, Seoul Medical Center, Seoul, South Korea 2 Department of Obstetrics and Gynecology, The Institute of Reproductive Medicine and Population, Medical Research Center, Seoul National University College of Medicine, Seoul, South Korea 3 Department of Obstetrics and Gynecology, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, South Korea 4 Department of Obstetrics and Gynecology, Chonnam National University College of Medicine, Gwangju, South Korea 5 Department of Obstetrics and Gynecology, St Vincent’s Hospital, College of Medicine, Catholic University of Korea, Seoul, South Korea
6 Correspondence address. Tel: +82-2-2072-2385; Fax: +82-2-762-3599; E-mail: ymchoi{at}snu.ac.kr
BACKGROUND: This study was performed to investigate whether specific haplotypes and several single nucleotide polymorphisms in the promoter region of the tumor necrosis factor (TNF)-
gene are associated with the risk of advanced stage endometriosis in a Korean population.
METHODS: This study comprised women with (n = 246) or without (n = 248) endometriosis. The TNF:g.[-1031T > C], TNF:g.[-863C > A] and TNF:g.[-857C > T] polymorphism in the TNF- gene were assessed by PCR-restriction fragment length polymorphism analysis, which utilized digestion by BbsI, HypCH4IV and HypCH4IV restriction enzymes, respectively. In silico haplotypes were deduced by using the Haploview version 3.32.
RESULTS: The genotype distribution of TNF:g.[-1031T > C] was significantly different between total endometriosis patients and the controls (T/T of 56.9 versus 60.1%, T/C of 35.4 versus 37.5% and C/C of 7.7 versus 2.4%, respectively, P = 0.027). This difference at the TNF:g.[-1031T > C] tends to increase in Stage IV endometriosis (P = 0.01). However, there was no difference in the TNF:g.[-863C > A] and TNF:g.[-857C > T] site between the two groups. Even when the endometriosis cases were subdivided into American Society for Reproductive Medicine Stages III and IV, genotype differences were not found. The CC homozygote at TNF:g.-863 was more frequently found in the controls than Non-CC group (P = 0.04; odds ratio = 0.67; 95% confidence interval = 0.45–0.98). All haplotypes and diplotypes, deduced by in silico analysis, showed no association with subgroups or controls.
CONCLUSIONS: Our results suggest that the genotype frequencies at the TNF:g.[-1031T > C] and the TNF:g.[-863C > A] sites may be associated with advanced stage endometriosis in the Korean population.
Key words: endometriosis/tumor necrosis factor/polymorphism
Submitted on September 30, 2007; resubmitted on December 21, 2007; accepted on January 11, 2008.
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