Leiomyoma (fibroids) is a type of malignant benign which is rooted in smooth muscles. The malignancy for the first time was described by Virchow in 1854 1. The most common malignant benign in female reproductive organ and it occurs in 20-50% of women above age of 30. The tumor is much more common in black people compared to white people. Masses with white completely definite limits are firm and grey white in slice 1,2.Although the molecular pathology is unknown, ULM has multifactorial etiology determined by both genetics and environmental factors has been defined. Women who have fibroids either have no symptoms or they see a doctor due to abnormal bleeding. The number and shape of leiomyoma is varied.
Uterine has three layers and depending on the layer on which fibroid is devloped, symptoms are different. Those developed in the uterine usually cause more bleeding. A number of them might extend out through the cervix and the patients see a doctor with complaints about a mass extrusion in vagina. Some leiomyomas are developed in uterine wall and cause swell in uterine. Some other fibroids are developed in outermost layer of uterine and cause swell in abdomen.
These leiomyomas can twist on their base and cause sudden chronic pain. It is not clear what causes these masses in uterine but the smooth muscles are known to be the root of such mass formation. Fortunately there is low probability of the masses getting malignant. There is only one tumor called leiomyomasarcoma which is malignant and causes indeterminate and abnormal bleeding and it has to be eliminated with surgery. The malignancy is determined by pathology examination of the sample 3. Methyl is one of the few enzymes that reduces catecholamines like dopamine and epinephrine and norepinephrine. In human body ctechol-O-methyl protein is coded by COMT gene 4.
It was discovered by a biochemist named Julius Axelrod in 1957. Methyl is involved in inactivating from catecholamine neurotransmitters (dopamine, epinephrine, norepi -O- catechole nephrine). This enzyme is a methyl group to catecholamine which through S-Andenosyl methionine (SAM) is introduced.
Each catechol mono structure like catecholestrogens and catechol flavonoids contain a layer of COMT. Lovodopa is a precursor to catecholamines and an important substrate to COMT. Val158Met polymorphism is a single-nucleotide polymorphism of the gene catechol-O-methyl that results in a valine to methonine mutation at position 158 (Val158Met) rs4680.
Another type of Val is catabolism dopamine which is four times the rate of its methionine counterpart 9. However, the met variant is overexpressed in brain, resulting in a 40% decrease in functional enzyme activity 10. The lower rates of catabolisis for the Met al.lele results in higher synaptic dopamine levels following neurotransmitter release, which ultimately results in decreasing dopaminergic stimulation of the post-synaptic neuro. Given the preferential role of COMT in prefrontal dopamine degradation, the Val158Met polymorphism is thought to has its effects on cognition by balancing dopamine signaling in the frontal lobes. Comparable effects on similar cognitive tasks, the frontal lobes, and the neurotransmitter dopamine have also all been linked to schizophrenia.2829 It has been proposed that an inherited variant of COMT is one of the genetic factors that may brings about the susceptibility of someone to developing schizophrenia later in life, naturally or due to adolescent-onset cannabis use 14. However, a more recent study shows that there is not such a significant connection between this gene and the effects of cannabis on schizophrenia development 15.
It is increasingly recognised that allelic variation at the COMT gene are also associated with emotional processing, because they seem to affect the interaction between prefrontal and limbic regions. Research conducted at the Section of Neurobiology of Psychosis, Institute of Psychiatry, King’s College London has illlusterated an effect of COMT both in patients with bipolar disorder and in their relatives 16 but these findings have not been repeated so far. The COMT Val158Met polymorphism also affects pleiotropic emotional processing.
17, 18. Ates in a research entitled “The Role of Polymorphism Catechol-O-Methyl transferase in Uterine Leiomyoma” studied 105 women suffering from malignant leiomyoma and 105 healthy post-menopausal women in Turkey and the research showed no significant association between polymorphism increase in COMT gene (rs4680; Val158Met) and higher risk of leiomyoma. Baird et al.. in research entitled “Growth of Uterine Leiomyoma among Premenopausal Black and White Women” state that the growth of uterine leiomyoma among African American women was 60% and the average age of patients was 35 and the growth in women from Caucasus was 40% with the average age of 35 26. Mayer et al.
in a study called “Uterine Fibroid Treatment” published a paper done in a research entitled “Ethnic Differences in Uterine Leiommyoma”, had mentioned the percent of uterine removal coordinating with annual age. The frequency in Black women was higher than white women. It is interesting that African American women have so far a higher frequency of genotype COMT 158 Val/Val (47%) and a lower frequency of COMT 158 Met/Met (5%).
However, white women have lower frequency of COMT 158 (19%) and a higher frequency of COMT 158 Met/Met (33 %) 28, 28. The findings in a study by Othman et al. in 2008 entitled “Molecular Genetics and Ethnic Differences in Fibroid Uterine” illustrated that the ethnic disparity in the incidence and biologic behaviors of ULM suggests that different races may show differences in estrogen metabolism.
These study results suggested that the regulation of COMT activity may indirectly balance the biologic effects of estrogen and play an etiological role in leiomyoma formation 29. Morikawa et al. in a research entitled “Association Study between Catechol-o-methyltransferase Polymorphisms and Uterine Leiomyomas in a Japanese Population” state that COMT gene polymorphisms do not seem to be related with ULM in a Japanese population30. In 2006 Denschlag showed that according to statistics, no significant differences regarding allele frequency and genotype distribution were noticed for COMT G158A in Caucasian women 31.
Gooden reported that no associations between fibroids and COM. Val158Met polymorphism were seen among African–American or white participants. Oliviera observed that there was no association between COMT Val158Met genotypes/alleles and ULM in Brazilian white/non-white women, but the study showed a noticeable relation between the COMT 158 Met al.lele and large fibroids.
These finding match our study conducted on the association of ULM and COMT G158A polymorphism with negative results except for the Al-Hendy study which showed that COMT Val/Val genotype is associated with the risk of ULM. Our study suggested that G158A polymorphism in the COMT gene is not connected with the susceptibility to ULM.