Tumor necrosis factor-alpha-308 promoter and p53 codon 72 gene polymorphisms in women with leiomyomas.
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.


METHODS
Prospective basic study.


METHODS
Departments of gynecology and genetics in a medical center.


METHODS
Group 1: leiomyoma (n = 159); group 2: non-leiomyoma (n = 131).


METHODS
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.


METHODS
Two gene polymorphisms were identified: [1] the A (cuttable)/G (uncuttable) polymorphisms of the TNF-alpha gene on chromosome 6p21.3; [2] A (cuttable)/P (uncuttable) polymorphisms of the p53 gene on chromosome 17p. Genotype and allelic frequencies in both groups were compared.


RESULTS
Genotype distribution and allele frequency of TNF-alpha 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%.


CONCLUSIONS
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.
Hsieh
Yao-Yuan
YY
Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung, Taiwan.
Chang
Chi-Chen
CC
Tsai
Fuu-Jen
FJ
Lin
Cheng-Chieh
CC
Yeh
Lian-Shun
LS
Tsai
Chang-Hai
CH
D000225:Adenine; D000483:Alleles; D016022:Case-Control Studies; D002886:Chromosomes, Human, Pair 17; D002896:Chromosomes, Human, Pair 6; D003062:Codon / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D016158:Genes, p53; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006147:Guanine; D006720:Homozygote; D006801:Humans; D007889:Leiomyoma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D014594:Uterine Neoplasms / Q000235:genetics*
D003062:Codon; D005819:Genetic Markers; D014409:Tumor Necrosis Factor-alpha; D006147:Guanine; D000225:Adenine