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Metabolizing Genes (metabolizing + gene)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Associations and Interactions Between SNPs in the Alcohol Metabolizing Genes and Alcoholism Phenotypes in European Americans

ALCOHOLISM, Issue 5 2009
Richard Sherva
Background:, Alcohol dependence is a major cause of morbidity and mortality worldwide and has a strong familial component. Several linkage and association studies have identified chromosomal regions and/or genes that affect alcohol consumption, notably in genes involved in the 2-stage pathway of alcohol metabolism. Methods:, Here, we use multiple regression models to test for associations and interactions between 2 alcohol-related phenotypes and SNPs in 17 genes involved in alcohol metabolism in a sample of 1,588 European American subjects. Results:, The strongest evidence for association after correcting for multiple testing was between rs1229984, a nonsynonymous coding SNP in ADH1B, and DSM-IV symptom count (p = 0.0003). This SNP was also associated with maximum number of drinks in 24 hours (p = 0.0004). Each minor allele at this SNP predicts 45% fewer DSM-IV symptoms and 18% fewer max drinks. Another SNP in a splice site in ALDH1A1 (rs8187974) showed evidence for association with both phenotypes as well (p = 0.02 and 0.004, respectively), but neither association was significant after accounting for multiple testing. Minor alleles at this SNP predict greater alcohol consumption. In addition, pairwise interactions were observed between SNPs in several genes (p = 0.00002). Conclusions:, We replicated the large effect of rs1229984 on alcohol behavior, and although not common (MAF = 4%), this polymorphism may be highly relevant from a public health perspective in European Americans. Another SNP, rs8187974, may also affect alcohol behavior but requires replication. Also, interactions between polymorphisms in genes involved in alcohol metabolism are likely determinants of the parameters that ultimately affect alcohol consumption. [source]

Genetic polymorphisms and susceptibility to childhood acute lymphoblastic leukemia

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2 2004
Renata Canalle
Abstract Acute lymphoblastic leukemia (ALL) is the most common form of pediatric cancer. Although exposure to environmental agents appears to predispose individuals to this disease, little attention has been paid to the role of genetic susceptibility to environmental exposures in the etiology of childhood ALL. The enzymes GSTM1, GSTT1, GSTP1, CYP1A1, and CYP2E1 are involved in the bioactivation and detoxification of a variety of xenobiotics present in food, organic solvents, tobacco smoke, drugs, alcoholic drinks, pesticides, and environmental pollutants. Polymorphisms in the genes coding for these enzymes have been associated with increased susceptibility to different cancers, including hematologic malignancies. To investigate whether these polymorphisms represent risk-modifying factors for childhood ALL, a study was conducted involving 113 Brazilian patients of childhood ALL and 221 controls with similar ethnic backgrounds. The data revealed that carriers of the rare GSTP1 Val allele were at higher risk of ALL (odds ratio [OR] = 2.7; 95% confidence interval [CI] = 1.1,6.8; P = 0.04). No difference was found in the prevalence of the GSTM1 and GSTT1 null genotypes between ALL patients and the controls, and no association was found between CYP1A1*2 and CYP2E1*3 variants and ALL. However, when the mutant CYP1A1 and CYP2E1 alleles were considered together with the GSTM1 and GSTP1 risk-elevating genotypes, the risk of ALL was increased further (OR = 10.3; 95% CI = 1.0,111.8; P = 0.05), suggesting a combined effect. These results imply that genetic variants of xenobiotic metabolizing genes influence the risk of developing childhood ALL. Environ. Mol. Mutagen. 43:100,109, 2004. © 2004 Wiley-Liss, Inc. [source]

Genetic polymorphisms in alcohol metabolism, alcohol intake and the risk of stomach cancer in Warsaw, Poland

INTERNATIONAL JOURNAL OF CANCER, Issue 9 2007
Fang Fang Zhang
Abstract Genetic variations increasing blood levels of acetaldehyde, the first metabolite of alcohol, refrain their carriers from drinking alcohol but may also put them at increased risk of cancer because of the mutagenic and carcinogenic effect of acetaldehyde. In a population-based study of 305 cases and 428 controls in Warsaw, Poland, we evaluated the effect of polymorphisms in alcohol metabolizing genes, including ADH1B (Ex9+5C>T, Ex3+23A>G, Ex3+58A>T and Ex9+77A>G), ADH1C (Ex8-56A>G and Ex6-14G>A) and ALDH2 (Ex1+82A>G), on levels of alcohol drinking and susceptibility of stomach cancer. We found that among control subjects frequency of alcohol drinking varied by alcohol metabolizing genotype. In particular, the weekly consumption of individuals carrying the AA, GA and GG genotypes of ALDH2 Ex1+82A >G polymorphism were 3.75, 2.26 and 1.53 drinks, respectively (p= 0.04). However, none of the assessed polymorphisms in these 3 genes had a measurable effect on stomach cancer risk. When stratified by ALDH2 Ex1+82A>G polymorphism, alcohol-related increases in stomach cancer risk were restricted to individuals with the AG/GG genotypes, with a more than 2-fold risk among daily drinkers (OR = 2.63, 95% CI = 1.00,6.88) and 3-fold risk (OR = 3.66, 95% CI = 1.19,11.24) among those with 40 or more drink-years. In summary, our results suggested that the ALDH2 Ex1+82 G allele may be functionally deficient in eliminating acetaldehyde and discourage alcohol drinking. Furthermore, heavy drinkers of alcohol who were genetically prone to accumulate acetaldehyde may face an increased risk of stomach cancer. © 2007 Wiley-Liss, Inc. [source]

Polymorphisms of drug-metabolizing genes and risk of non-Hodgkin lymphoma,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 12 2009
Hee Nam Kim
Drug metabolizing genes are involved in the detoxification of chemical carcinogens. Polymorphisms in drug-metabolizing genes affect the risk of some forms of cancer. We analyzed six polymorphisms to evaluate their association with risk for non-Hodgkin lymphoma (NHL), and to examine whether smoking modifies these associations in population-based study in Korea (713 cases and 1,700 controls). The GSTP1 rs1695 AG and the combined AG/GG genotypes were associated with decreased risk of NHL (odds ratio (OR)AG = 0.67, 95% confidence interval (CI) = 0.55,0.82; ORAG/GG = 0.66, 95% CI = 0.54,0.80) and DLBCL (ORAG = 0.63, 95% CI = 0.49,0.82; ORAG/GG = 0.64, 95% CI = 0.50,0.82). For T-cell lymphoma, only the combined AG/GG genotype was associated with decreased risk (ORAG/GG = 0.65, 95% CI = 0.44,0.96). The CYP1A1 rs1048943 AG genotype and the combined AG/GG genotypes were associated with increased risk of NHL (ORAG = 1.28, 95% CI = 1.07,1.54; ORAG/GG = 1.26, 95% CI = 1.06,1.51) and DLBCL (ORAG = 1.32, 95% CI = 1.04,1.66; ORAG/GG = 1.30, 95% CI = 1.03,1.63), but not T-cell lymphoma. Smoking does not modify the association between these polymorphisms and NHL risk. Our data provide evidence that the GSTP1 rs1695 and the CYP1A1 rs1048943 genotypes affect the risk of NHL in Korea. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc. [source]