Cytochrome P450 1A1 Gene Polymorphisms Research Articles

Association of Interleukin-10 Vitamin D Receptor and Cytochrome P450 1A1 Gene Polymorphisms with Renal Cell Carcinoma Risk

The current study examined the relationship between renal cell carcinoma-related risk and gene polymorphisms in the interleukin-10, vitamin D receptor and cytochrome P450 1A1 genes. Using the preferred reporting items for systematic reviews and meta-analyses criteria, the link between gene polymorphisms and renal cell carcinoma was studied by utilizing the Web of Science, Embase, PubMed and Wanfang databases. The CC and TT genotypes along with the interleukin-10-819C/T C-allele were found to be substantially associated with renal cell carcinoma risk in the Chinese residents. Furthermore, significant relationships between the vitamin D receptor, FokI FF genotype and FokI F allele, ApaI A allele, ApaI AA and aa genotypes and renal cell carcinoma risk were observed in Asian populations. The cytochrome P450 1A1 MspI (rs4646903) polymorphism was substantially linked to an elevated risk of renal cell carcinoma in the T allele, TT genotype. However, no significant relationships were found between renal cell carcinoma risk and the single nucleotide polymorphisms interleukin-10-1082A/G, vitamin D receptor TaqI and cytochrome P450 1A1 Ile462Val (rs1544410).

Cytochrome P450 1A1 gene polymorphisms and cervical cancer risk: A systematic review and meta-analysis.

Objective:This meta-analysis aims to examine whether the MspI and Ile462Val polymorphisms of cytochrome P450 1A1 (CYP1A1) are associated with cervical cancer risk.Methods:Eligible case–control studies were identified dated until July 2017. Pooled odds ratios (ORs) were used to assess the strength of the association between the two variants and cervical cancer risk.Results:Thirteen studies were eligible (2148 cases and 2252 controls) concerning MspI polymorphism and 8 studies were eligible (1466 cases and 1690 controls) for Ile462Val polymorphism. MspI polymorphism seemed to result in cervical cancer risk in any genetic model (C allele vs T allele: OR = 1.44, 95% confidence interval [CI] = 1.16–1.79; heterozygous model: OR = 1.40, 95% CI = 1.08–1.82; homozygous model: OR = 2.22, 95% CI = 1.48–3.33, dominant model: OR = 1.50, 95% CI = 1.14–1.98 and recessive model: OR = 1.80, 95% CI = 1.35–2.41); similar significantly increased risk was found among Caucasians and Asians. Ile462Val polymorphism was associated with elevated cervical cancer risk (Val allele vs Ile allele: OR = 1.85, 95% CI = 1.27–2.67; heterozygous model: OR = 1.42, 95% CI = 1.28–1.61; homozygous model: OR = 2.94, 95% CI = 1.15–7.54; dominant model: OR = 2.00, 95% CI = 1.33–3.00); this finding was replicated upon Caucasian population.Conclusion:This meta-analysis demonstrated that polymorphisms in MspI and Ile462Val of CYP1A1 were risk factors for developing cervical cancer.

Potential Positive Association between Cytochrome P450 1A1 Gene Polymorphisms and Recurrent Pregnancy Loss: a Meta-Analysis.

In order to discover the potential genetic risks associated with recurrent pregnancy loss (RPL), this meta-analysis was conducted to assess the association between CYP1A1 gene polymorphism and RPL. Studies were retrieved from the databases PubMed, Embase, HuGENet, and CNKI. Four models were then applied. Seven studies, including three datasets for the rs1048943 and five for the rs4646903 single-nucleotide polymorphism (SNP), were included in this analysis, involving 613 cases and 398 controls for the rs1048943; and 864 cases and 842 controls for the rs4646903 SNP. After comprehensive analysis, we found that rs4646903 was significantly associated with RPL [recessive (OR= 1.72, 95%CI: 1.13-2.61); codominant (CC vs TT; OR = 1.74, 95%CI: 1.12-2.71), (CC vs CT; OR = 1.67, 95%CI: 1.07-2.62) and allele analysis (OR = 1.27, 95%CI: 1.07-1.50)]. In the following subgroup analysis, a positive association was also discovered among people of Asian descent, especially South Asians. However, there was no obvious association between rs1048943 and RPL. In summary, our results suggest that CYP1A1 gene polymorphism (particularly for rs4646903) might be associated with RPL risk, especially among South Asians. Further studies are required to confirm this association.

Combination effect of cytochrome P450 1A1 gene polymorphisms on uterine leiomyoma: A case-control study.

Uterine leiomyoma (UL) is an estrogen-dependent neoplasm of the uterus, and estrogen metabolizing enzymes affect its progression. This study aimed to evaluate the association between two single-nucleotide polymorphisms of cytochrome P450 1A1 (CYP1A1) gene and UL risk. The study consisted of 105 patients with UL and 112 healthy women as controls. Ile462Val (A/G) and Asp449Asp (T/C) polymorphisms of CYP1A1 gene were analyzed by DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism methods, respectively. The findings indicated no association between Ile462Val (A/G) and Asp449Asp (T/C) polymorphisms of CYP1A1 gene and UL (p < 0.05). However, the combination effect of TT/AG genotypes of the Asp449Asp (T/C) and Ile462Val (A/G) polymorphisms was associated with 4.3-fold higher risk of UL. In addition, haplotype analysis revealed that TG haplotype of the Asp449Asp (T/C) and Ile462Val (A/G) polymorphisms could increase the UL risk nearly 4.9-fold. Asp449Asp (T/C) and Ile462Val (A/G) polymorphisms of CYP1A1 gene were not associated with UL susceptibility; however, the combination of the TT/AG genotypes and TG haplotype could increase the UL risk.

Genetic Polymorphisms of Cytochrome P4501A1 (CYP1A1) and Glutathione S-Transferase P1 (GSTP1) and Risk of Hepatocellular Carcinoma Among Chronic Hepatitis C Patients in Egypt.

Cytochrome P450 1A1 (CYP1A1) and Glutathione S-transferase P1 (GSTP1) genes are involved in the metabolism of many carcinogens. Polymorphisms in these genes with altered enzyme activity have been reported. The present study evaluated the synergistic effect between CYP1A1 and GSTP1 gene polymorphisms and smoking on development of HCV-related liver disease and hepatocellular carcinoma (HCC). The patients group comprised 40 patients with HCC and 40 patients with liver cirrhosis. The control group comprised 40 healthy subjects having no history of malignancy. The genetic polymorphisms were studied using polymerase chain reaction restriction fragment length polymorphism (PCR RFLP) technique on blood samples. The number of current or former smoker among HCC and cirrhotic patients as well as the median Pack/year of cigarette smoked were significantly higher in HCC and liver cirrhotic patients than in control group. Subjects with CYP1A1 gene variants (m1 and m3) had no significant risk to develop cirrhosis or HCC compared to control group. Individuals carrying the Ile/Val genotype of GSTP1 had a significant increased risk of HCC (OR of 2.2, 95% CI 1.143-4.261) and had larger tumor size. No significant risk was observed on combining both genes variants or on combining smoking with variants of both genes. In conclusion, the GSTP1 Ile/Val genotype and Val allele are associated with an increased risk of HCC. CYP1A1 and GSTP1 genes variants interaction did not increase the risk of HCC.

Effect of CYP1A1 gene polymorphism and psychological distress on seminal analysis parameters.

BackgroundPsychological factor alters fertility hormones and contributes to male infertility. Anxiety and depression are common manifestations of psychological distress. Cytochrome P-4501A1 (CYP1A1) metabolizes xenobiotics and fertility hormones that influence male fertility. The effect of CYP1A1 polymorphism on male fertility has remained controversial.The present study was designed to assess the effect of psychological distress and CYP1A1 polymorphisms and their interactions on parameters of seminal analysis.MethodsEighty male partners of infertile couples were evaluated for level of distress using Hospital anxiety and depression score (HADS) questionnaire. As per WHO guidelines (2010), sperm count, motility and morphology were assessed and subjects were classified as (a) subjects having normal sperm characteristics and (b) subjects having abnormal sperm characteristics. CYP1A1 polymorphisms were detected by ASO-PCR.ResultsThe significant odd’s ratio indicates that psychological distress (OR:10.54; CI:3.72–29.84; P < 0.001), CYP1A1*4(OR:10.31; CI:3.01–35.24; P < 0.001) and CYP1A1*2C (OR:7.01; CI:1.78–27.56; P = 0.002) polymorphisms are risk factors for the development of abnormal sperm characteristics in male subjects. Data analysis with two way ANOVA shows that psychological distress, CYP1A1*4 and CYP1A1*2C polymorphisms significantly affect but do not interact among them to influence sperm parameters.ConclusionsIt is concluded that CYP1A1 gene polymorphisms and psychological distress act independently but do not interact with each other in pathogenesis of male infertility.

Association of CYP1A1, GSTM1 and GSTT1 gene polymorphisms with risk of non-small cell lung cancer in Andhra Pradesh region of South India.

BackgroundLung cancer is one of the most preventable causes of death globally both in developed and developing countries. Although it is well established that smokers develop lung cancer, there are some smokers who are free from the disease risk. The predisposition to lung cancer is attributed to genetic polymorphisms in xenobiotic metabolizing genes. Reports on assessment of xenobiotic metabolizing genes like Cytochrome P 450 1A1 (CYP1A1), Glutathione -S -transferase M1 (GSTM1) and T1 (GSTT1) polymorphisms from India are meagre, and reports from Andhra Pradesh are lacking.Methods and resultsAssessment of polymorphisms in CYP1A1, GSTM1 and GSTT1 in NSCLC patients and healthy individuals specific to population of Andhra Pradesh, a South Indian state was attempted by multiplex PCR and RFLP, and this is the first study which tried to correlate oxidative stress with the polymorphisms in xenobiotic metabolizing genes. Results showed that CYP1A1 m1 ‘CC’ genotype was significantly associated with lung cancer susceptibility with a 2.3-fold risk, CYP1A1 m2 ‘AG’ gene polymorphisms with 8.8-fold risk and GSTT1 (−/−) genotype demonstrated a twofold risk of disease susceptibility.ConclusionsA combined role of genetic polymorphisms and smoking status can be attributed for the cause of lung cancer. Further, the association between oxidative stress and genetic polymorphisms showed a correlation between GSTT1 and super oxide dismutase activity; CYP1A1 m1, m2 and GSTT1 with glutathione peroxidase activity; CYP1A1 m1 and GSTM1 with melondialdehyde levels; and CYP1A1 m1 and GSTT1 with 8-oxo-7,8-dihydro-2′-deoxyguanosine. A higher risk of lung cancer seems to be associated with combined gene polymorphisms of phase I and phase II enzymes than that ascribed to single gene polymorphism.Electronic supplementary materialThe online version of this article (doi:10.1186/s40001-016-0209-x) contains supplementary material, which is available to authorized users.

Effect of CYP1A1 and GSTM1 genetic polymorphisms on bone tumor susceptibility.

Tumor gene polymorphisms are often associated with individual susceptibility to genetic diseases. Cytochrome P4501A1 (CYP1A1) and glutathione S-transferase mu 1 (GSTM1) gene polymorphisms are closely related to the susceptibility of the body to chemical carcinogens in the environment. Therefore, we explored the relationship between CYP1A1 and GSTM1 gene polymorphisms and susceptibility to bone tumors. Multiplex-polymerase chain reaction (PCR), allelic-specific PCR, and PCR-restriction fragment length polymorphism techniques were used to analyze CYP1A1 and GSTM1 gene polymorphisms in 52 bone tumor patients and 100 healthy subjects. The allelic variation frequency of the CYP1A1 gene at exon 7 (Ile 462 Val) in bone tumor patients was 0.462, which was significantly higher than that in the normal controls (0.223). The frequency of the absence of the GSTM1 homozygous genotype in the patients (0.65) was also markedly higher than that in the control group (0.41). Subjects with CYP1A1 Val/Val homozygous mutations and absence of the GSTM1 homozygous genotype were at markedly increased risk of developing bone tumors [ORs 4.15 (95%CI: 1.268-13.30) and 2.35 (95%CI: 1.15-4.85), respectively]. The OR for the combined effect of the CYP1A1 and GSTM1 gene polymorphisms was 8.55 (95%CI: 1.75-41.50). CYP1A1 and GSTM1 polymorphisms are genetic risk factors in patients with bone tumors, and the allelic variation of these genes increases the risk of bone tumor occurrence.

AB210. The cytochrome P4501A1 gene polymorphisms and idiopathic male infertility risk: a meta-analysis

Meta-analysis Polymorphism Studies of the relationship between male infertility and CYP1A1 polymorphisms are inconclusive. To drive a more precise estimation, we performed a meta-analysis based on 1,060 cases and 1,225 controls from 7 published case-control studies. PubMed and CNKI literature search were conducted to identify all eligible studies investigating such a relationship. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the additive model, dominant model, recessive model, and allele-frequency genetic model. In the overall analysis, the frequency of CYP1A1*2A genotype was significantly associated with susceptibility to idiopathic male infertility. Further stratified analysis by ethnicity showed notable association between the polymorphism and risk of idiopathic male infertility in Asians. In conclusion, these results support that the CYP1A1*2A genotype polymorphism mainly contributes to idiopathic male infertility susceptibility in Asians but not in Caucasians.

Does CYP1A1 gene polymorphism affect cell damage biomarkers and ageing?

This study aimed to investigate the effects of cytochrome P450 1A1 (CYP1A1) gene polymorphism on early ageing due to occupational exposure to mutagens. The project was conducted on buccal epithelial cells collected from mechanical-workshop workers and controls. Epithelial cells were obtained from the inner part of the cheeks. Techniques including comet assay, micronuclei test, real-time polymerase chain reaction, and restriction fragment length polymorphism-polymerase chain reaction were used to assess DNA damage biomarkers. The results showed that there was a significant difference in relative telomere length (P = 0.039) between wild and mutated genotypes among all individuals. Furthermore, occupational exposure showed no statistically significant effects on biomarkers of the possible influences of gene polymorphism and different rates of ageing among workers (P > 0.05), except for relative telomere length (P = 0.041) among workers as a whole. It was concluded that the effects of occupational exposure to mutagens on genetic material in buccal cells mediated by CYP1A1 gene polymorphism were not significant. In addition, CYP1A1 gene polymorphism might have a protective effect against premature ageing due to occupational exposure to mutagenic chemicals.

Cytochrome P450 1A1 Gene Polymorphisms and Endometrial Cancer Risk: A Meta-Analysis

This meta-analysis aims to examine whether the genotype status of Msp1, Ile462Val, and Thr461Asn polymorphisms in cytochrome P450 1A1 (CYP1A1) is associated with endometrial cancer risk. Eligible case-control studies were identified through search in MEDLINE (end of search: August 2010). Pooled odds ratios (ORs) were appropriately derived from fixed-effects or random-effects models. Concerning MspI polymorphism, 8 studies were eligible (1456 cases and 2371 controls); 9 studies were eligible (1889 cases and 3662 controls) for Ile462Val and 6 studies were eligible (1272 cases and 2122 controls) for Thr461Asn. MspI polymorphism was not associated with endometrial cancer risk (for heterozygous TC vs TT carriers: OR = 0.83, 95% confidence interval [CI], 0.59-1.15, random effects; for homozygous CC vs TT carriers: OR = 1.00, 95% CI, 0.55-1.82, fixed effects). Similarly, Ile462Val polymorphism was not associated with endometrial cancer risk (for heterozygous Ile/Val vs Ile/Ile carriers: OR = 1.27, 95% CI, 0.78-2.06, random effects; for homozygous Val/Val vs Ile/Ile carriers: OR = 1.16, 95% CI, 0.48-2.81, fixed effects). Accordingly, Thr461Asn status was not significantly associated with endometrial cancer risk. The same results were reproduced in Caucasians. The 3 examined CYP1A1 genotype polymorphisms do not seem to confer any additional risk for endometrial cancer in Caucasians. Accumulation of further data seems mandatory for future race-specific analyses.

CYP1A1 gene polymorphism and polycystic ovary syndrome

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).

CYP1A1 Gene Polymorphisms in Modifying the Association Between Passive Smoking and Primary Dysmenorrhea

This study investigated whether the association between passive smoking exposure and primary dysmenorrhea is modified by two susceptibility genes, cytochrome P450 1A1 (CYP1A1)MspI and CYP1A1HincII. We recruited 1645 female textile workers from 1997 to 2000 in Anqing, China, collecting information about passive smoking and status of primary dysmenorrhea and taking blood samples. We analyzed the association of CYP1A1 gene polymorphisms and passive smoking exposure with primary dysmenorrhea using multiple logistic regression. In the passive smoking group, women who had the C/C6235 genotype (odds ratio [OR] = 1.8; 95% confidence intervals [CI] = 1.0-3.3) in CYP1A1MspI and Ile/Ile462 genotype (OR = 2.9; 95% CI = 1.1-7.7) in CYP1A1HincII had increased risk of dysmenorrhea. When stratified by genotype, the adjusted OR of dysmenorrhea was 1.6 (95% CI = 1.2-2.1) for the passive smoking group with the Ile/Ile462 genotype and 1.5 (95% CI = 1.0-2.1) with the C/C6235 genotype, compared with the nonpassive smoking group. The data further showed that there was a significant combined effect between passive smoking and the CYP1A1MspI C/C6235 and HincII Ile/Ile462 genotypes (OR = 2.4; 95% CI = 1.2-4.9). CYP1A1MspI and HincII genotypes modified the association between passive smoking and primary dysmenorrhea.

A case-control study on the impact of cytochrome P450 2E1 and 1A1 gene polymorphisms on the risk of lung can- cer of the Han nationality in Guangzhou district

Most of the researches about lung cancer have focused on the polymorphisms of single gene rather than the cooperation of the genes. The aim of this study is to investigate the correlation of gene polymorphisms of cytochrome P450 2E1 (CYP2E1) Rsa I and cytochrome P450 1A1 (CYP1A1) independently and in combination with the risk of lung cancer. A case-control study which included 91 lung cancer cases and 91 hospital-based controls was carried out, and all of them were the Han nationality in Guangzhou district. Blood samples were collected for detecting CYP2E1 Rsa I and CYP1A1 gene polymorphisms by polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLP). No significant difference was observed in genotype frequencies of CYP2E1 Rsa I and CYP1A1 Msp I between case and control groups. Odd ratio was 5.48 and 1.51 respectively without significant difference (P > 0.05). Individuals with CYP2E1 Rsa I C1C1 and CYP1A1 m2m2 genotype had 3.00-fold risk of developing lung cancer compared with those who had CYP2E1 Rsa I C1C2 and CYP1A1 m1m1 genotype (P < 0.05, 95% CI 1.03-8.78). Single polymorphism of CYP2E1 and CYP1A1 doesn't increase the risk of developing lung cancer, but the combination of two genetic polymorphisms significantly increases the risk of developing lung cancer.

CYP1A1 gene polymorphism and risk of endometrial hyperplasia and endometrial carcinoma

The cytochrome P4501A1 (CYP1A1) is involved in the metabolism of environmental carcinogens and estrogen. We hypothesized that CYP1A1 genetic polymorphism may be a susceptibility factor for endometrial hyperplasia (EH) and endometrial carcinoma (ECa). We therefore evaluated this hypothesis in patients with EH and ECa and control subjects using allele-specific polymerase chain reaction-based method in a Turkish population. The patients with CYP1A1 Ile/Val genotype had a fivefold higher risk of having EH than those with Ile/Ile. In contrast, a higher frequency of any Val genotype (Ile/Val and Val/Val) was found in patients with EH, indicating that persons carrying any Val allele are at increased risk for developing EH. In the ECa group, patients were also more likely to have CYP1A1 Ile/Val allele, with an adjusted odds ratio of 3.0. Moreover, there was a statistically significant increase in relative risk association with any Val genotype between patients and controls, suggesting that individuals carrying any Val genotype are at increased risk for developing ECa. We concluded that variant alleles of the CYP1A1 gene might be associated with EH and ECa susceptibility. Further studies with a large sample size should be considered to address issues of interactions between CYP1A1 and other risk factors.

CYP1A1 gene polymorphism and risk of endometrial hyperplasia and endometrial carcinoma

The cytochrome P4501A1 (CYP1A1) is involved in the metabolism of environmental carcinogens and estrogen. We hypothesized that CYP1A1 genetic polymorphism may be a susceptibility factor for endometrial hyperplasia (EH) and endometrial carcinoma (ECa). We therefore evaluated this hypothesis in patients with EH and ECa and control subjects using allele-specific polymerase chain reaction–based method in a Turkish population. The patients with CYP1A1 Ile/Val genotype had a fivefold higher risk of having EH than those with Ile/Ile. In contrast, a higher frequency of any Val genotype (Ile/Val and Val/Val) was found in patients with EH, indicating that persons carrying any Val allele are at increased risk for developing EH. In the ECa group, patients were also more likely to have CYP1A1 Ile/Val allele, with an adjusted odds ratio of 3.0. Moreover, there was a statistically significant increase in relative risk association with any Val genotype between patients and controls, suggesting that individuals carrying any Val genotype are at increased risk for developing ECa. We concluded that variant alleles of the CYP1A1 gene might be associated with EH and ECa susceptibility. Further studies with a large sample size should be considered to address issues of interactions between CYP1A1 and other risk factors.

Possible risk modification by CYP1A1, GSTM1 and GSTT1 gene polymorphisms in lung cancer susceptibility in a South Indian population

Susceptibility to lung cancer has been shown to be modulated by inheritance of polymorphic genes encoding cytochrome P450 1A1 (CYP1A1) and glutathione S transferases (GSTM1 and GSTT1), which are involved in the bioactivation and detoxification of environmental toxins. As the incidence of lung cancer is known to differ according to ethnicity, we have conducted a case-control study of 146 South Indian lung cancer patients along with 146 healthy controls, to assess any association between CYP1A1, GSTM1 and GSTT1 polymorphisms, either separately or in combination, with the likelihood of development of lung cancer in our population. The current weight of evidence from our study indicated that the frequency of CYP1A1 MspI homozygous variant alleles was significantly higher in cases (OR = 3.178). We observed a considerable difference in the GSTT1 null deletion frequency in this population when compared with other populations (OR = 2.472, 95% CI: 1.191-5.094, P = 0.014). There was no relative risk in GSTM1 null genotype when analysed singly (P = 0.453). Considering genotype combinations, risk of lung cancer increased remarkably significantly in individuals having one variant allele of CYP1A1, GSTM1, or GSTT1, suggesting gene-gene interactions. Rare genotypic combinations (such as CYP1A1 wild GSTM1 or GSTT1 either null; CYP1A1 variant both GSTM1 and GSTT1 present; CYP1A1 variant GSTM1 or GSTT1 either null), were at higher risk compared to the reference group. Moreover, patients who had smoked <20 pack years and harboured the CYP1A1 variant allele or the GSTT1 null genotype also had a significant risk of lung cancer. Hence our study-the first to analyse a South Indian population-suggests the importance of combined CYP1A1, GSTM1 and GSTT1 polymorphisms in the development of smoking-induced lung cancer.

Cytochrome P-450 1A1 Gene Polymorphisms and Risk of Breast Cancer: A HuGE Review

Cytochrome P-450 (CYP) 1A1 plays a key role in phase I metabolism of polycyclic aromatic hydrocarbons and in estrogen metabolism. It is expressed predominantly in extrahepatic tissues, including the breast. Four CYP1A1 gene polymorphisms (3801T --> C, Ile462Val, 3205T --> C, and Thr461Asp) have been studied in relation to breast cancer. The 3801C variant is more common than the Val variant. Both variants occur more frequently in Asians than in White populations. The 3205T --> C polymorphism has been observed in African Americans only. Little data are available on the geographic/ethnic distribution of the Thr461Asp polymorphism. The functional significance of the polymorphisms is unclear. In 17 studies, no consistent association between breast cancer and CYP1A1 genotype was found. Meta-analysis found no significant risk for the genotypes 1) 3801C/C (relative risk (RR) = 0.97, 95% confidence interval (CI): 0.52, 1.80) or 3801T/C (RR = 0.91, 95% CI: 0.70, 1.19) versus 3801T/T, 2) Val/Val (RR = 1.04, 95% CI: 0.63, 1.74) or Ile/Val (RR = 0.92, 95% CI: 0.76, 1.10) versus Ile/Ile, or 3) Asp/Asp (RR = 0.95, 95% CI: 0.20, 4.49) or Thr/Asp (RR = 1.12, 95% CI: 0.87, 1.43) versus Thr/Thr. Future studies should explore possible interactions between CYP1A1 and sources of polycyclic aromatic hydrocarbons, markers of estrogen exposure, other lifestyle factors influencing hormonal levels, and other genes involved in polycyclic aromatic hydrocarbon metabolism or hormonal biosynthesis.

The cytochrome P4501A1 T6325C polymorphism is associated with the risk of hypertension

Cytochrome P4501A1 (CYP1A1) catalyses the hydroxylation of estradiol and arachidonic acid (AA) producing vasoactive substances, such as catecholestrogens and eicosanoids. Estrogens and eicosanoids are considered to be involved in the pathophysiology of hypertension. However the role of Cytochrome P4501A1 activity in the pathophysiology of hypertension is unclear. CYP1A1 has been known to express genetic variance. Some of its polymorphisms are associated with changes in Cytochrome P4501A1 activity. The C allele of T6325C and the G allele of A4889G polymorphisms have been associated with elevated cytochrome P4501A1 activity. We hypothesized that CYP1A1 polymorphisms would be associated with the risk of hypertension.The hypothesis was tested through a case control study in 208 control and 75 hypertensive male and female subjects. Diabetes and thyroid disease were exclusion factors. We determined the genotype for three CYP1A1 polymorphisms (T6325C, A4889G, and C4887A), using PCR-RFLP, in our population. We observed that the C allele of the CYP1A1 T6325C polymorphism was associated with hypertension (p=0.008, chi-square test). The odds ratio was 2.3 with a 95% confidence interval of 1.3 to 4.1. No association was found between the two other CYP1A1 gene polymorphisms and hypertension. These results implicate the C allele of the CYP1A1 T6325C polymorphism as a risk factor for the development of hypertension and suggest that the activity of cytochrome P4501A1 may play a role in the pathophysiology of this disease.

Cytochrome p450 1A1 gene polymorphisms in patients with psoriatic arthritis

Objective: To investigate the associations of cytochrome p450 1A1 (CYP1A1) gene polymorphisms with susceptibility to psoriatic arthritis in Taiwan.Methods: CYP 1A1 gene polymorphisms were determined in 52 patients with psoriatic arthritis and in 90 healthy controls by polymerase chain reaction/restriction fragment length polymorphism.Results: The genotype frequency of CYP1A1 4889A/G was significantly increased in patients with psoriatic arthritis in comparison with healthy controls. The phenotype frequency of CYP1A1 4889G was also significantly increased in patients with psoriatic arthritis. The genotype frequency of CYP1A1 4887C/A was significantly higher in patients with psoriatic arthritis than in controls. The allele and phenotype frequencies of 4887A were also significantly increased in patients with psoriatic arthritis. We also found that the association of CYP1A1 4887A with psoriatic arthritis was independent of 4889G but a synergistic effect was present between CYP1A1 4887A and 4889G. The CYP1A1 4889A/G and 4887C/A polymorphisms were not associated with the manifestations and severity of psoriatic arthritis.Conclusion: CYP1A1 4887A and 4889G may be precipitating factors for susceptibility to psoriatic arthritis in Taiwan. An additive effect was found between CYP1A1 4887A and 4889G.