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Cytochrome P450c17 alpha 5'-untranslated region T/C polymorphism in endometriosis
(2004-08-01)
Hsieh, YY
;
Chang, CC
;
Tsai, FJ
;
Lini, CC
;
Tsai, CH
Estrogen plays a role in the pathogenesis of endometriosis. The CYP17 gene codes for the cytochrome P450cl7alpha enzyme that is involved in the estrogen biosynthesis. We aimed to investigate if CYP 17 polymorphism could be used as marker to predict the susceptibility of endometriosis. Women were divided into two groups: (1) severe endometriosis (n= 119); (2) non-endometriosis groups (n=1 28). A 169-bp fragment encompassing the T/C polymorphic site in 5'-untranslated promoter region (5'-UTR) of the CYP17 was amplified by the polymerase chain reaction, treated with restriction enzyme MspA1I, and electrophoresis. The polymorphism was divided into restriction- enzyme indigestible (T homozygote), T/C heterozygote, and digestible (C homozygote). Genotypes and allelic frequencies for this polymorphism in both groups were compared. We observed a higher but non-significant percentage of T homozygote in the endometriosis women compared with the non-endometriosis women. Proportions of T homozygote/heterozygote/C homozygote for CYP17 in both groups were: (1) 26.1/46.2/27.7% and (2) 17.2/45.3/37.5% (p- value=0.13 1). T allele was related with higher susceptibility of endometriosis. T and C allele frequencies in both groups were: (1) 49.2/50.8%; (2) 39.8/60.2% (p- value=0.046). Despite the CYP17* T allele Appearing to be asscoiated with a trend of increased risk of endometriosis, CYP17 5'-UTR gene polymorphism might not be a useful marker for prediction of endometriosis susceptibility.
Tumor necrosis factor-alpha-308 promoter and p53 codon 72 gene polymorphisms in women with leiomyomas
(2004-10-01)
Hsieh, YY
;
Chang, CC
;
Tsai, FJ
;
Lin, CC
;
Yeh, LS
Objective: Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, plays an important role in the process of autoimmune diseases. p53 is related to the regulation of cell growth and prevention of carcinogenesis. We propose to investigate whether gene polymorphisms for TNF-alpha-308 promoter and p53 could be used as markers of susceptibility in leiomyomas. Design: Prospective basic study. Setting: Departments of gynecology and genetics in a medical center. Patient(s): Group 1: leiomyoma (n = 159); group 2: non-leiomyoma (n = 13 1). Intervention(s): Genomic DNA was obtained from peripheral leukocyte. The TNF-alpha and p53 gene polymorphisms were amplified by polymerase chain reaction (PCR), enzyme restriction, and electrophoresis. Main Outcome Measure(s): Two gene polymorphisms were identified: [1] the A (cuttable)/G (uncuttable) polymorphisms of the TNF-alpha gene on chromosome 6p2l.3; [2] A (cuttable)/P (uncuttable) polymorphisms of the p53 gene on chromosome 17p. Genotype and allelic frequencies in both groups were compared. Result(s): Genotype distribution and allele frequency of TNF-a gene polymorphism in both groups were significantly different. Proportions of A homozygote/heterozygote/G homozygote for TNF-alpha in both groups were: (group 1) 61%/34.6%/4.4% and (group 2) 81.7%/14.5%/3.8%. Proportions of allele A/G for TNF-alpha in both groups were: (group 1) 78.3%/21.7% and (group 2) 88.9%/11.1%. Distributions of p53 polymorphisms in both groups were not different. The proportions of A homozygotes/heterozygotes/P homozygotes for p53 were (group 1) 32.7%/42.1%/25.2% and (group 2) 28.2%/48.9%/22.9%. Conclusion(s): G homozygote and G allele for TNF-alpha promoter are related to a higher risk of leiomyomas. The p53 codon 72 gene polymorphism is not associated with the susceptibility of leiomyomas. (C) 2004 by American Society for Reproductive Medicine.
Estrogen receptor alpha dinucleotide repeat and cytochrorne P450c17 alpha gene polymorphisms are associated with susceptibility to endometriosis
(2005-03-01)
Hsieh, YY
;
Chang, CC
;
Tsai, FJ
;
Lin, CC
;
Tsai, CH
Objective: To investigate the association of endometriosis with estrogen receptor alpha (ER alpha) and cytochrome P450c17 alpha (CYP17) gene polymorphisms in light of the fact that estrogen plays a role in the pathogenesis of endometriosis and the CYP17 enzyme is involved with estrogen biosynthesis. Design: Prospective study. Setting: Genetics and gynecology units. Patient(s): All patients were divided into two groups: group 1, women with endometriosis (n = 119); group 2, normal controls (n = 108). Intervention(s): A dinucleotide (thymine-adenine [TA]) repeat polymorphism lying upstream of the ER alpha gene and A1/A2 polymorphism of the CYP17 gene were amplified by polymerase chain reaction, enzyme restriction, and electrophoresis. Main Outcome Measure(s): The ER Genotypes were classified into A through T (TA repeats, 10-29). The CYP17 genotypes included indigestible (A1 homozygote), heterozygote, and digestible (A2, homozygote). We compared these polymorphism distributions in both groups. Result(s): The percentage of genotypes D-G (TA, 13-16) in both groups were 110.5%, 29.4%, 13.0%, and 11.3% in group 1 and 7.9%, 16.7% 19.9%, and 17.6% in group 2. The genotype E (14 TA repeats) is associated with a higher risk of endometriosis. Proportions of Al homozygote/heterozygote/A2 homozygote for CYP17 were 26.1%/46.2%/27.7% for Group I and 14.8%/44.5%/40.7% for group 2, respectively. The Al homozygote and allele were associated with a higher susceptibility of endornetriosis. Conclusion(s): ER alpha* 14 TA repeats and the CYP17* Al allele are associated with an increased risk of endometriosis. Both polymorphisms are useful markers for predicting endometriosis susceptibility. (Fertil Steril (R) 2005:83:567-72. (c) 2005 by American Society for Reproductive Medicine.)

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