Val153Met Polymorphism of Catechol-O-Methyltransferase and Prevalence of Uterine Leiomyomata

Abstract

The catechol-O-methyltransferase (COMT) gene encodes enzymes that inactivate catechol estrogens and may have a protective role in estrogen-induced tumorigenesis, such as uterine leiomyoma (fibroids). Val158Met is a common single-nucleotide polymorphism of the COMT gene (Ex4-12 G>A; rs4680) that results in a lower activity enzyme, increasing susceptibility to tumorigenesis. The purpose of this study was to evaluate the relation between the COMTVal158Met polymorphism and uterine fibroids. Participants were 972 premenopausal African American (n = 576) and white (n = 396) women from a cross-sectional sample of women in the National Institute of Environmental Health Science's Uterine Fibroid Study. Blood was collected from participants for DNA, and telephone interviews and questionnaires were completed to gather demographic and reproductive history. Prevalence ratios and 95% confidence intervals were estimated using race-specific log-risk regression models. Effect measure modification by age, body mass index, oral contraceptive use, full-term births, smoking, and alcohol use were also evaluated. Distributions of genotypes and fibroid prevalence varied by race. No associations between fibroids and Val158Met were observed among African American or white participants. This study suggests that variation in this polymorphism alone does not affect fibroid prevalence. Additional research is needed to examine other variations and haplotypes within the COMT gene.

A Multicenter Case-Control Study on Screening of Single Nucleotide Polymorphisms in Estrogen-Metabolizing Enzymes and Susceptibility to Uterine Leiomyoma in Han Chinese

“…Semiquinones, quinones, and radicals cause genomic mutations and cell damage. The mechanisms of COMT in hormone-dependent UL reported in previous studies are generally accepted [15,16]. At least 8 SNP loci can be found in the coding region of COMT gene.…”

The associations between the Val158Met in the catechol-O-methyltransferase (COMT) gene and the risk of uterine leiomyoma (ULM)

“…A large number of genes have been suggested to be associated with risk of ULM, and the COMT gene is one of them (Cong et al, 2012;Huang et al, 2010;Je et al, 2012). The Val158Met polymorphism in the COMT gene has been identified to be associated with risk of ULM, but the results were inconclusive (Al-Hendy and Salama, 2006b; Denschlag et al, 2006;Gooden et al, 2007). In addition, there is still no meta-analysis to investigate these associations.…”

“…Carriage of the mutant COMT G1947A allele results in a 3-4 fold lower enzyme activity of COMT (Lachman et al, 1996). Many studies have suggested that the Val158Met polymorphism was associated with susceptibility to ULM (Al-Hendy and Salama, 2006b;Denschlag et al, 2006;Gooden et al, 2007); however, the results were inconclusive, especially in populations from different ethnical backgrounds. Meta-analysis is a useful method for investigating associations between genetic factors and diseases (Cao et al, 2013;Chen et al, 2013;Nie et al, 2013), because it uses a quantitative approach to combine the results of different studies on the same topic, and potentially provide more reliable conclusions.…”

“…Then, one article was excluded for not being the Val158Met polymorphism of COMT gene (Jin, 2008). Finally, a total of 12 case-control studies in 7 articles concerning 1506 cases and 1243 controls were included in the meta-analysis (Al-Hendy and Salama, 2006b; Ates et al, 2013;de Oliveira et al, 2008;Denschlag et al, 2006;Gooden et al, 2007;Ivanova et al, 2010;Morikawa et al, 2008). The characteristics and genotype distributions of included studies were listed in Table 1.…”

Fibroid growth and medical options for treatment

“…Tumoral molecular biology studies suggest that E 2 metabolism may be altered in women of African origin, because polymorphism in the catecholamine-O-methyl transferase (COMT) gene leading to reduced enzyme activity has been correlated with increased tumor size (53). However, this polymorphism does not appear to alter fibroid prevalence (54). The product of E 2 transformation by COMT, 2-methoxy-E 2 , has been shown to be involved in the regulation of aromatase activity and estrogen signaling in fibroids.…”