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Relevant Polymorphisms (relevant + polymorphism)
Selected AbstractsComorbidity of Alcohol Dependence With Attention-Deficit Hyperactivity Disorder: Differences in Phenotype With Increased Severity of the Substance Disorder, but Not in Genotype (Serotonin Transporter and 5-Hydroxytryptamine-2c Receptor)ALCOHOLISM, Issue 10 2003Monika Johann Background: Nearly 50% of subjects with continuing symptoms of attention-deficit hyperactivity disorder (ADHD) in adulthood have been reported to show a comorbid substance use disorder. Both ADHD and alcohol dependence have a high genetic load and might even share overlapping sources of genetic liability. Recently, the functional relevant polymorphism within the promoter region of the serotonin transporter gene (5-HTT) and the 5-hydroxytryptamine-2c (5-HT2c) receptor Cys23Ser have been proposed as candidate genes for both entities. Methods: We investigated phenotype and 5-HTT/5-HT2c genotype characteristics in 314 alcoholics of German descent. Results: There was no significant difference in 5-HTT genotype or 5-HT2c allele distribution between alcoholics and matched controls. Sixty-seven alcoholics fulfilled DSM-IV criteria of ADHD with ongoing symptoms in adulthood and had a Wender Utah Rating Scale score greater than 90. Thirty had ADHD plus antisocial personality disorder. The subgroup of alcoholics with ADHD (ADHD+) showed a significantly higher daily and record ethanol intake per month, an earlier age at onset of alcohol dependence, and a higher frequency of suicidal ideation, court proceedings, and antisocial personality disorder. In our sample, more than 50% of type 2 alcoholics according to Cloninger consist of the ADHD+ and/or antisocial personality disorder-positive subjects. There were no differences in 5-HTT genotype or 5-HT2c allele distribution between the ADHD+ subgroups and alcoholics without comorbidity and matched controls, respectively. Conclusions: Comorbidity of alcoholism and ADHD forms a distinct phenotype that shows an increased severity of the substance disorder. This phenotype contributes substantially to the so-called type 2 alcoholics according to Cloninger. In our sample, the functional relevant 5-HTT promoter and the 5-HT2c receptor Cys23Ser polymorphism do not contribute to the supposed common genetic predisposition of ADHD and alcohol dependence. [source] Further evidence for an association between the gamma-aminobutyric acid receptor A, subunit 4 genes on chromosome 4 and Fagerström Test for Nicotine DependenceADDICTION, Issue 3 2009Arpana Agrawal ABSTRACT Aims A previous association analysis identified polymorphisms in gamma-aminobutyric acid receptor A, subunit 4 (GABRA4) and GABRA2 to be associated with nicotine dependence, as assessed by a score of 4 or more on the Fagerström Test for Nicotine Dependence (FTND). In the present report, we extend the previous study by expanding our genotyping efforts significantly for these two genes. Design In 1049 cases (FTND of 4 or more) and 872 controls (smokers with FTND of 0) from the United States and Australia, we examine the association between 23 GABRA4 and 39 GABRA2 recently genotyped single nucleotide polymorphisms (SNPs) and nicotine dependence using logistic regression-based association analyses using the genomic analysis package PLINK. Results Two and 18 additional SNPs in GABRA4 and GABRA2, respectively, were associated with nicotine dependence. The SNPs identified in GABRA4 (P -value = 0.002) were restricted to introns 1 and 2, exon 1 and the 5, end of the gene, while those in GABRA2 localized to the 3, end of the gene and spanned introns 9,3, and were in moderate to high linkage disequilibrium (as measured by r2) with each other and with previously studied polymorphisms. Conclusion Our findings demonstrate consistently the role of GABRA4 and GABRA2 in nicotine dependence. However, further research is needed to identify the biological influence of these intronic variations and to isolate functionally relevant polymorphisms neighboring them. [source] Association of polymorphisms in the interleukin-18 gene in patients with Crohn's disease depending on the CARD15/NOD2 genotypeINFLAMMATORY BOWEL DISEASES, Issue 12 2005Jürgen Glas MD Abstract Background: An increased expression of interleukin-18 (IL-18), a proinflammatory cytokine inducing interferon-,, has been found in Crohn's disease (CD). In the IL-18 gene, several partly functional relevant polymorphisms are known. This study sought to investigate associations of IL-18 polymorphisms in inflammatory bowel disease and CD according to CARD15/NOD2 mutation status and clinical phenotypes. Methods: The IL-18 polymorphisms ,607, ,137, and the third position of codon 35 (c35/3) were genotyped in 210 patients with CD, 140 patients with ulcerative colitis, and 265 healthy controls using polymerase chain reaction and restriction fragment length polymorphism analysis. Results: Frequencies of alleles and genotypes of the 3 polymorphisms and of the respective haplotypes and diplotypes displayed no significant differences between the whole groups of patients with CD and ulcerative colitis, respectively, compared with the controls. After stratification of patients with CD for CARD15/NOD2 status, significant associations of genotypes ,137 CC (P = 0.018) and c35/3 CC (P = 0.010) and of the diplotype 2-2 (P = 0.018) were found in cases carrying CARD15/NOD2 mutations. Associations of genotypes ,137 GG (P = 0.015) and c35/3 AA (P = 0.030) with colonic disease only in cases positive for CARD15/NOD2 mutations and of the genotype ,607 AA (P = 0.007) with fistulas in cases negative for CARD15/NOD2 mutations were observed. Conclusions: In this study, significant differences of several genotypes and diplotypes within the IL-18 gene in CD depending on CARD15/NOD2 status have been found. In context with an increased expression of IL-18 in CD, it remains to be shown whether the expression of IL-18 is influenced by CARD15/NOD2 mutation status. [source] Polymorphisms of the IL-1 Gene Complex Are Associated With Alcohol Dependence in Spanish Caucasians: Data From an Association StudyALCOHOLISM, Issue 12 2009Pilar A. Saiz Background:, There is growing evidence for involvement of pro-inflammatory cytokines in alcohol dependence. The aim of this study was to investigate whether 4 functionally relevant polymorphisms of the interleukin-1 (IL-1) and tumor necrosis factor-alpha genes were associated with alcohol dependence and with measures of clinical severity and treatment outcome. Methods:, Two hundred alcohol-dependent (AD) patients and 420 healthy controls from the same Spanish Caucasian population were genotyped using standard methods. Baseline and 6-month assessments included alcohol intake, addiction severity, and biomarkers of alcohol intake. Results:, Alcohol-dependent patients showed an excess of IL-1,,889 C/T [50.8% vs. 39.3%, ,2 (df) = 7.30 (2), uncorrected p = 0.026, corrected p = 0.104] and IL-1RA (86 bp)n A1/A1 genotypes [64.8% vs. 50.8%, ,2 (df) = 12.65 (3), corrected p = 0.020]. The A1/A1 excess was associated with alcohol dependence only in men [69.9% vs. 49.5%, ,2 (df) = 15.72 (2), corrected p < 0.001]. Six-month clinical and hematological outcome measures did not vary by genotype of the 4 polymorphisms. Haplotype analysis revealed an excess of the IL-1,,889 C/IL-1, +3953 C/IL-1RA A2 haplotype in the control group compared with AD patients [20.0% vs. 14.1%, ,2 (df) = 7.25 (1), p = 0.007; odds ratio (OR) = 0.64, 95% confidence interval (CI) = 0.46,0.89] and in the abstainers after 6 months of treatment compared with nonabstinent patients [14.7% vs. 6.2%, ,2 (df) = 5.65 (1), p = 0.017; OR = 2.56, 95% CI = 1.15,5.62]. Conclusions:, Our findings provide further tentative evidence of the role of IL-1 in alcohol dependence as well as evidence that the nature of the associations may be direct, gender-specific, or involve haplotype effects. However, findings from single association studies constitute tentative knowledge and must be interpreted carefully and precise replication is required. [source] | ||||||||||