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Functional Genetic Polymorphisms (functional + genetic_polymorphism)
Selected AbstractsAssociation Between the Functional Polymorphism of Catechol- O -Methyltransferase Gene and Alcohol Consumption Among Social DrinkersALCOHOLISM, Issue 2 2000Jussi Kauhanen Background: A common functional genetic polymorphism in the catechol- O -methyltransferase (COMT) gene (Val158 Met) results in 3- to 4-fold differences in COMT enzyme activity and dopamine inactivation rate. Previous studies have shown that type I alcoholism is more common among subjects with low activity COMT genotype (LL), compared with high activity (HH) or heterozygotic (LH) genotypes. Methods: We studied alcohol consumption and the COMT genotype in middle-aged Finnish men (n= 896), who represented an unselected ethnically homogenous population sample and reported using alcohol during the past year. Average alcohol use in pure ethanol (grams per week) was compared between subjects with LL genotype and subjects with LH or HH genotypes. Results: Men with LL genotype (30% of all subjects) reported 27% higher weekly alcohol consumption compared with the two other genotype groups (p < 0.05). The difference remained statistically significant after a multivariate adjustment for sociodemographic factors and prior or existing diseases (p= 0.031). Conclusions: The results indicate that COMT polymorphism may contribute significantly to alcohol intake not only in alcoholics but also in a general male population. [source] Increased cerebral activity in Parkinson's disease patients carrying the DRD2 TaqIA A1 allele during a demanding motor task: a compensatory mechanism?GENES, BRAIN AND BEHAVIOR, Issue 6 2007D. Bartrés-Faz Previous studies suggest that neuroimaging techniques are useful for detecting the effects of functional genetic polymorphisms on brain function in healthy subjects or in patients presenting with psychiatric or neurodegenerative conditions. Former evidence showed that individuals carrying risk alleles displayed broader patterns of brain activity during behavioural and cognitive tasks, despite being clinically comparable to non-carriers. This suggests the presence of compensatory brain mechanisms. In the present study, we investigated this effect in Parkinson's disease (PD) patients carrying the DRD2 TaqIA A1 allelic variant. This variant may confer an increased risk of developing the disease and/or influence the clinical presentation. During a complex sequential motor task, we evidenced by functional magnetic resonance imaging that A1 allele carriers activated a larger network of bilateral cerebral areas than non-carriers, including cerebellar and premotor regions. Both groups had similar clinical and demographic measures. In addition, their motor performance during the functional magnetic resonance experiment was comparable. Therefore, our conclusions, pending replication in a larger sample, seem to reflect the recruitment of compensatory cerebral resources during motor processing in PD patients carrying the A1 allele. [source] COX-2 polymorphisms and the risk for head and neck cancer in white patientsHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 7 2009Wilbert H. M. Peters PhD Abstract Background. Cyclooxygenase-2 (COX-2) is an enzyme involved in the synthesis of prostaglandins and thromboxanes, which are regulators of processes such as inflammation, cell proliferation, and angiogenesis, all relevant for cancer development. We investigated whether functional genetic polymorphisms in COX-2 may have a risk-modifying effect on head and neck carcinogenesis. Methods. Blood from 431 white patients with oral, pharyngeal, or laryngeal carcinoma and 438 white healthy controls was investigated for the presence of 2 functional promoter region polymorphisms (,1195A,G and ,765G,C) in COX-2. Results. Logistic regression analysis did not show differences in COX-2 genotype distributions between patients and controls. Also no differences were found when stratified according to tumor localization, sex, or tobacco consumption. Conclusion. In contrast to earlier reports on the role of these COX-2 polymorphisms in mediating susceptibility to squamous esophageal carcinoma in a Chinese population, we could not demonstrate a risk-modifying effect in head and neck carcinogenesis in whites. © 2009 Wiley Periodicals, Inc. Head Neck, 2009 [source] Microsomal epoxide hydrolase genotypes and the risk for head and neck cancerHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 7 2008Martin Lacko MD Abstract Background. Microsomal epoxide hydrolase (mEH) is an enzyme involved in the metabolism of (pre)carcinogens in tobacco smoke. We investigated whether functional genetic polymorphisms in mEH may have a risk-modifying effect on head and neck carcinogenesis. Methods. Blood from 429 patients with oral, pharyngeal, and laryngeal carcinoma and 419 healthy subjects was investigated for mEH polymorphisms. Results. Logistic regression analysis did not show differences in mEH genotype distributions between patients and controls, when categorized according to predicted mEH enzyme activity. Also no differences were found when evaluated according to tumor localization, sex, or tobacco consumption. A significantly higher incidence of the 139Arg/Arg variant was found in patients with hypopharyngeal carcinoma compared with controls (OR = 4.39, 95% CI = 1.45 to 13.35). Conclusion. In contrast to earlier reports, we could not demonstrate a risk-modifying effect of genetic polymorphisms in mEH on head and neck carcinogenesis, except for the predicted high activity variant in patients with hypopharyngeal carcinoma. © 2008 Wiley Periodicals, Inc. Head Neck 2008 [source] Polymorphisms in PTGS1, PTGS2 and IL-10 do not influence colorectal adenoma recurrence in the context of a randomized aspirin intervention trialINTERNATIONAL JOURNAL OF CANCER, Issue 9 2007Richard A. Hubner Abstract Regular use of aspirin and other nonsteroidal antiinflammatory drugs reduces both the development of colorectal neoplasia and recurrence of colorectal adenoma (CRA). Modulation of the effects of aspirin by genetic factors has been reported, potentially allowing targeting of treatment to individuals most likely to gain benefit. Prostaglandin H synthase 1 (PTGS1) and PTGS2 are key enzymes in prostaglandin synthesis and are inhibited by aspirin, whilst interleukin-10 (IL-10) is an important antiinflammatory cytokine. We investigated whether functional genetic polymorphisms in the PTGS1, PTGS2 and IL-10 genes influence CRA recurrence in individuals participating in a randomized aspirin intervention trial. DNA was available for genotyping from 546 patients who received aspirin (300 mg daily) or placebo for a mean 41-months' duration. Homozygote carriers of variant alleles for the PTGS1 50C>T, PTGS2 ,765G>C and IL-10 ,592C>A polymorphisms did not have a significantly altered risk of CRA recurrence (relative risk [RR] = 0.91; 95% confidence interval [CI]: 0.14,6.07, RR = 1.32; 95%CI: 0.66,2.62 and RR = 1.24; 95% CI: 0.74,2.07, respectively). There were also no significant interactions between aspirin intervention and genotype in determining recurrence risk. These data indicate that these polymorphisms are unlikely to influence CRA recurrence and cannot be used to identify individuals who derive benefit from aspirin intervention. © 2007 Wiley-Liss, Inc. [source] Host,bacterial interaction in the development of gastric precancerous lesions in a high risk population for gastric cancer in Venezuela,INTERNATIONAL JOURNAL OF CANCER, Issue 7 2006Ikuko Kato Abstract Helicobacter pylori (HP) infection affects over 50% of the world's population. The prevalence is over 90% in populations at high risk for gastric cancer, but clinical outcomes of the infection are highly variable and thus host genetic factors have been suggested to play a role in its outcomes in addition to bacterial factors. In this study, we examined the effects of common functional genetic polymorphisms of several proinflammatory cytokines known to be overexpressed in HP-infected gastric mucosa on the risk of various stages of gastric premalignant lesions. The odds ratios (ORs) and 95% confidence intervals (CI) for atrophic gastritis, intestinal metaplasia and dysplasia were estimated by multinominal logistic regression analysis among 2,033 Venezuelan subjects. There was a significant effect of IL8 -251A allele on the prevalence of dysplasia (p = 0.021). The OR associated with the A-allele was 1.34 (95% CI: 0.82,2.18) for heterozygotes and 2.00 (95% CI: 1.13,3.56) for homozygotes, compared with the TT genotype. Furthermore, there was a statistically significant interaction between the number of A-alleles and HP cag A genotype (p = 0.009), suggesting that the A-allele increased the risk of dysplasia only when cag A was present. The OR for the AA compared with TT genotype was 3.22 (95% CI: 1.60,6.52) in this group. There were no associations with other proinflammatory cytokines studied, i.e., IL1,, IL6, monocyte chemoattractant protein 1 (MCP1) and TNF,, or with other stages of premalignant lesions. The present study provides important evidence suggesting host,bacterial interactions in the development of gastric precancerous lesions. © 2006 Wiley-Liss, Inc. [source] | ||||||||||