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General Comment |
NCBI Summary:
This gene, CYP1A1, encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and its expression is induced by some polycyclic aromatic hydrocarbons (PAHs), some of which are found in cigarette smoke. The enzyme's endogenous substrate is unknown; however, it is able to metabolize some PAHs to carcinogenic intermediates. The gene has been associated with lung cancer risk. A related family member, CYP1A2, is located approximately 25 kb away from CYP1A1 on chromosome 15. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jan 2016]
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Comment |
CONSTITUTIVE EXPRESSION OF CYP1A1 IN BOVINE CUMULUS OOCYTE-COMPLEXES IN VITRO: MECHANISMS AND BIOLOGICAL IMPLICATIONS.
The arylhydrocarbon receptor (AhR) is known to mediate toxic responses to dioxin (TCDD) and related compounds and has been extensively characterized from a toxicological viewpoint. However, it has been recently reported that the AhR may have a central role in ovarian physiology. To investigate the role of AhR during oocyte maturation, Pocar P, et al 2004
analyzed the expression of AhR, its nuclear partner ARNT and the major target gene CYP1A1, in bovine cumulus-oocyte complexes (COCs) by semi-quantitative RT-PCR and Western blot. Co-expression of AhR and ARNT was observed in both oocytes and surrounding cumulus cells before and after in vitro maturation (IVM). Furthermore, after IVM both cell types showed a clear up-regulation of AhR mRNA compared with the expression at 0 h. Constitutive expression of CYP1A1 mRNA was observed in immature oocytes at background level, whereas no expression was observed in the surrounding cumulus cells. Interestingly, a significative increase of CYP1A1 expression level was observed in both oocytes and cumulus cells after IVM. To further investigate the role of AhR in CYP1A1 up-regulation and in oocyte maturation, COCs were treated throughout IVM with the AhR antagonists' alpha-naphthoflavone and resveratrol. Both antagonists decreased the level of CYP1A1 in COCs compared with controls. Furthermore, CYP1A1 down-regulation was accompanied by a reduced ability of oocytes to complete in vitro maturation until metaphase II stage. These results suggest that CYP1A1 induction in COCs is necessary for the correct proceeding of the in vitro oocyte maturation in bovine and suggest a physiological role of AhR during resumption of meiosis.
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Comment |
2-Methoxyestradiol in the human corpus luteum throughout the luteal phase and its influence on lutein cell steroidogenesis and?angiogenic activity. Kohen P 2013 et al.
OBJECTIVE
To quantitate 2-methoxyestradiol (2-ME) in human corpus luteum (CL) of different ages and to determine the expression of cytochrome-P450-1A1 (CYP1A1) and catechol-O-methyl transferase (COMT) in CL and the action of 2-ME on P, vascular endothelial growth factor (VEGF) secretion, and luteal angiogenesis.
DESIGN
Experimental study.
SETTING
University division of reproductive endocrinology.
PATIENT(S)
Twenty-four women of reproductive age.
INTERVENTION(S)
CL was collected from 15 women during the minilaparotomy for tubal sterilization. Granulosa lutein cells were harvested 36 hours after hCG administration in patients undergoing IVF.
MAIN OUTCOMES MEASURE(S)
Levels of 2-ME were determined by high-performance liquid chromatography in CL. CYP1A1 and COMT were assessed by immunohistochemistry and Western blot. P and VEGF were measured by radioimmunoassay and ELISA. The angiogenic potential was analyzed using EA.hy926 cells.
RESULT(S)
Plasma levels of E2 decreased in the late luteal phase in association with an increase in luteal tissue of 2-ME concentrations. Concomitantly, there was a significant reduction of angiogenic activity in late CL. There was no significant variation in CYP1A1 and COMT expression in all CL. In physiological doses, 2-ME inhibited basal VEGF by granulosa lutein cells and diminished the angiogenic activity in conditioned media but did not prevent P and VEGF production stimulated by hCG.
CONCLUSION(S)
These data suggest the participation of 2-ME in physiological luteolysis by reducing angiogenesis. However, 2-ME did not prevent in?vitro hCG stimulation of P biosynthesis, providing a mechanism for CL rescue in the cycle of conception.
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Mutations |
3 mutations
Species: human
Mutation name: None
type: naturally occurring
fertility: subfertile
Comment: CYP1A1 gene polymorphism and polycystic ovary syndrome. Esinler I et al. The aim of this study was to assess the rates of variant alleles of cytochrome P4501A1 (CYP1A1) in patients with polycystic ovary syndrome (PCOS). It was designed as a case-control study in Hacettepe University, Faculty of Medicine, Department of Obstetrics and Gynecology and Genetics. Forty-eight patients with PCOS served as the study group. Ninety-six regularly cycling women with no clinical and biochemical evidence of hyperandrogenism and polycystic ovary appearance served as the controls. The CYP1A1 variant alleles of all patients were determined via polymerase chain reaction. The rate of the CYP1A1 isoleucine (Ile)/valine (Val) allele was significantly higher in patients with PCOS than in the controls (OR: 7.8, 95% CI: 3.45-17.52, P < 0.001). However, there was no statistically significant difference in the distribution of Val/Val genotype (OR: 4.0, 95% CI: 0.60-26.73). The rate of any Val genotype (Ile/Val or Val/Val) was significantly higher in patients with PCOS compared with the control group (OR: 7.4, 95% CI: 3.33-16.46, P < 0.001). In conclusion, the patients with PCOS had a 7.8-fold higher frequency of CYP1A1 Ile/Val genotype and a 7.4-fold higher frequency of CYP1A1 of any Val genotype (Ile/Val or Val/Val).
Species: human
Mutation name: None
type: naturally occurring
fertility: subfertile
Comment: CYP1A1 polymorphism in adolescents with polycystic ovary syndrome. Akg?t al. OBJECTIVE: To evaluate the rates of the CYP1A1 Ile/Val polymorphism in Turkish adolescent females. METHODS: The CYP1A1 Ile/Val polymorphism was analyzed by collecting DNA samples from 44 adolescents with polycystic ovary syndrome (PCOS)-according to the Rotterdam criteria-and 120 healthy female controls aged 13-18years in Ankara, Turkey. RESULTS: There was a 2.5-fold increase in the frequency of the CYP1A1 Ile/Val genotype in adolescents with PCOS compared with the control group (odds ratio [OR] 2.54; 95% confidence interval [CI], 1.143-5.637; P<0.001), in addition to a 2.4-fold increase in the frequency of the Val allele (OR 2.43; 95% CI, 1.099-5.397; P<0.001). CONCLUSION: The data show an association between CYP1A1 and PCOS, indicating that variant alleles of the gene may affect the metabolic and transport pathway of estrogens, thus causing PCOS.
Species: human
Mutation name: None
type: naturally occurring
fertility: subfertile
Comment: Common polymorphisms in the CYP1A1 and CYP11A1 genes and polycystic ovary syndrome risk: a meta-analysis and meta-regression. Shen W 2013 et al.
AIM
Increasing scientific evidences suggest that common polymorphisms in the CYP1A1 and CYP11A1 genes may contribute to the development and progression of polycystic ovary syndrome (PCOS), but many existing studies have yielded inconclusive results. The aim of this study was to perform a meta-analysis of published studies on the associations between common polymorphisms in the CYP1A1 and CYP11A1 genes and susceptibility to PCOS.
METHODS
An extensive literature search for relevant studies was conducted on PubMed, Embase, Web of Science, Cochrane Library, and CBM databases from their inception through 1 June, 2013. This meta-analysis was performed using the STATA 12.0 software. The crude risk ratio (RR) with 95?% confidence interval was calculated.
RESULTS
Thirteen case-control studies were included in this meta-analysis with a total of 1,571 PCOS cases and 1,918 healthy controls. Our meta-analysis revealed that CYP1A1 MspI (rs4646903 T?>?C) polymorphism may increase the risk of PCOS, especially among Caucasian populations. Furthermore, CYP11A1 microsatellite [TTTA]n repeat polymorphism also showed significant associations with increased risk of PCOS among Caucasian populations. However, there was no statistically significant association between CYP1A1 Ile462Val (rs1048943 A?>?G) polymorphism and PCOS risk.
CONCLUSION
Our meta-analysis suggests that CYP1A1 MspI and CYP11A1 microsatellite [TTTA]n repeat polymorphisms may contribute to increasing susceptibility to PCOS among Caucasian populations. Detection of common polymorphisms in the CYP1A1 and CYP11A1 genes might be promising biomarkers for the diagnosis and prognosis of PCOS.
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