Serotonin receptor (5HTR2A) gene polymorphism has been reported to be associated with clinical phenotypes in schizophrenia. The current study attempted to investigate a relationship between 5HTR2A 102T/C polymorphism and personality traits as well as clinical symptoms in patients with ICD-10 diagnoses of schizophrenia and affective disorders. 5HTR2A genotyping, clinical and psychological assessment were administered to 375 patients, 104 first-degree healthy relatives of the patients and 157 controls. In the patients an association was observed between the 2/2 5HTR2A genotype and scores on the Hypochondriasis scale (MMPI) (ANOVA, F = 4.56; P = 0.011) and trait anxiety (F = 4.21; P = 0.002). A significant difference between 1/1 and 2/2 genotypes has been also found for Neuroticism scores (EPI) (t = 2.18; P = 0.0031). No significant differences by 5HTR2A genotype were observed in either the control or first-degree relatives group for all scales studied. Positive, negative and psychopathological symptoms emerged higher in the 2/2 genotype patients compared to other genotype carriers. Therefore, the 2/2 genotype may contribute to produce the phenotype, with specific clinical and pathological features in common, regardless of nosologic heterogeneity of psychoses.
Mutations in the superoxide dismutase (SOD1) gene have been linked to amyotrophic lateral sclerosis (ALS). A 50 base pair (bp) deletion of SOD1 has been suggested to reduce transcription and to be associated with later disease onset in ALS. This study was aimed to reveal if the 50?bp deletion influenced SOD1 enzymatic activity, occurrence and phenotype of the disease in a Swedish ALS/control cohort. Blood samples from 512 Swedish ALS patients and 354 Swedish controls without coding SOD1 mutations were analysed for the 50?bp deletion allele. The enzymatic activity of SOD1 in erythrocytes was analysed and genotype-phenotype correlations were assessed. Results demonstrated that the genotype frequencies of the 50?bp deletion were all found to be in Hardy-Weinberg equilibrium. No significant differences were found for age of onset, disease duration or site of onset. SOD1 enzymatic activity showed a statistically significant decreasing trend in the control group, in which the allele was associated with a 5% reduction in SOD1 activity. The results suggest that the 50?bp deletion has a moderate reducing effect on SOD1 synthesis. No modulating effects, however, were found on ALS onset, phenotype and survival in the Swedish population.
In this study, evaluation of genome instability in individuals exposed to chemical compounds included detection of the genetic polymorphism of some xenobiotic metabolic enzymes (CYP1A1, CYP1E1, PON1, GSTM1, GSTT1), as well as measurement of oxidative state chemiluminescent variables and the level of cytogenetic damage. According to the study, the level of chromosomal aberrations in peripheral blood lymphocytes shows a strong correlation with PON54 left allele and GSTM1 null genotype, and can be described by the polynomial function of blood plasma luminol-dependent chemiluminescence. The frequencies of micronuclei in buccal epithelium displayed a weak association with GSTT1 null genotype.
Apolipoprotein C-III (apoC-III) is the major component of triglyceride-rich lipoproteins. One of six identified polymorphisms in the apoC-III 5'-untranslated region (T-455C) is located within a functional insulin-response element. In a group of 137 elderly individuals (70-106 years old), the allele distribution was analyzed using restriction fragment length polymorphisms. Statistical analysis of allele frequencies was performed on subgroups selected by age and in elderly patients with arterial hypertension or ischemic heart disease. A greater frequency of the apoC-III -455C allele was demonstrated with aging (p
OBJECTIVE: To study the contribution of aggrecan VNTR (variable number of tandem repeats) polymorphism to clinically differing manifestations of hand osteoarthritis (OA). DESIGN: Five hundred thirty Finnish females representing two academically similar occupations with completely diverse exposure to hand load were included. Radiographs of hands were analysed, the OA findings were graded and the subjects were divided into categories. Aggrecan VNTR alleles were identified by Southern hybridization. Statistical analyses were used to compare joint involvement and pathological findings with the prevalences of the alleles and genotypes. RESULTS: Subjects homozygous for the most common aggrecan VNTR allele, A27 with 27 repeats, had a significantly lower risk of hand OA, with OR 0.46 (95% CI 0.27-0.78) for OA of grade 2 or more. Our results suggest that carrying two copies of the alleles with less than 27 repeats could predispose a subject to a severe hand OA (OR 2.45, 95% CI 1.17-5.12) and carrying two copies of the alleles with more than 27 repeats also increases the risk of the disease (OR 1.73, 95% CI 1.03-2.89). CONCLUSIONS: These findings indicate that allele A27 provides protection from hand OA and that alleles shorter or longer than this may predispose subjects to the disease. Furthermore, they suggest that a certain number of tandem repeats provide for optimal functioning of the aggrecan molecule and that the contribution of genetic factors to the development of hand OA may be even more important than that of environmental factors.
Department of Pathophysiology, Department of Phthisiology and Pulmonology, Siberian State Medical University, Federal Agency of Health Care and Social Development, Tomsk, Russia. firstname.lastname@example.org
Modern immunological and molecular genetic studies showed that tuberculosis is accompanied by an imbalance in the production of immunoregulatory cytokines by mononuclear leukocytes. T allele and homozygous TT genotype of T-330G polymorphism in the IL2 gene, T allele and TT genotype of C-590T polymorphism in the IL4 gene, and CC genotype of A-1188C polymorphism in the IL12B gene are immunogenetic factors that have protective activity against susceptibility to pulmonary tuberculosis. Susceptibility to tuberculous infection is associated with A1A2 genotype of the polymorphic region +3953 A1/A2 in the IL1B gene; G allele and TG and GG genotypes of T-330G polymorphism in the IL2 gene; C allele and CC and CT genotypes of C-590T polymorphism in the IL4 gene; and AC genotype of the polymorphic region A-1188C in the IL12 gene.
Among adrenergic receptor subtypes that regulate lipid mobilization, the alpha2-adrenergic receptor is involved in the inhibition of fatty acid mobilization from adipose tissue. A C-1291G polymorphism is located in the alpha2-adrenergic receptor gene (ADRA2A) but no association with body fat accumulation has been reported yet.
Body mass index (BMI), fat mass (FAT), percentage body fat (%FAT), trunk-to-extremity skinfold ratio (TER), sum of eight skinfolds (SF8), and abdominal subcutaneous (ASF), visceral (AVF), and total (ATF) fat areas assessed by CT scan have been measured in adult sedentary white (n = 503) and black (n = 276) subjects participating in the HERITAGE Family Study. Association between the C-1291G polymorphism and each phenotype was tested separately in men and women of each race using ANCOVA with the effects of age as covariate in addition to the effects of BMI for TER and of FAT for AVF, ASF, and ATF.
The allele frequencies of the ADRA2A C-1291G polymorphism differed between races. No association was observed in white subjects, except for a moderate effect of the polymorphism accounting for less than 1% of the variance in AVF and ATF in women. In black subjects, however, the G-1291 allele was found to be associated with an increase of TER in men (3.8% of variance accounted for by the polymorphism), while in black women it was associated with a decrease in TER (2.9%) and in AVF (2.5%).
These results suggest a role for the ADRA2A gene in determining the propensity to store fat in the abdominal area, independently of total body fatness.
Neurotensin is a 13-amino acid neuropeptide that endogenously modulates dopamine release in the central nervous system. In substance dependence, the mesolimbic dopamine system has been postulated to be a central structure that mediates rewarding and reinforcing effects. Neurotensin receptors in the neurons of the ventral tegmental area facilitate dopamine release, making the neurotensin gene an excellent candidate gene for alcohol dependence and for other behaviors that involve reinforcement.
A total of 639 psychiatrically interviewed Finns were genotyped for proneurotensin 479A>G polymorphism. We used the polymorphism as a marker to study the association between proneurotensin gene and alcohol dependence by comparing 229 unrelated Finnish healthy controls to 134 unrelated alcohol-dependent (DSM-III-R criteria) subjects who were also criminal offenders. In addition, 276 relatives of the alcohol-dependent and control subjects were genotyped.
The frequencies of the genotypes in the whole sample (n = 639) were 0.84 for 479A/A, 0.16 for 479A/G, and 0.003 for 479G/G. The frequency of the rarer 479G allele was 0.07 and 0.06 in controls and alcohol-dependent subjects, respectively, and this difference was not statistically significant (chi2 = 0.264, df = 1, p = 0.61, controls vs. alcohol-dependent subjects).
The results of the comparison between psychiatrically interviewed controls and alcoholics from a relatively well defined population indicate that the proneurotensin 479A>G polymorphism is not strongly associated with alcohol dependence. The results do not rule out a role for this gene in the pathogenesis of alcoholism or in differential vulnerability.
AIMS: To examine whether polymorphic variants of the HTR2C gene are associated with diagnosis of alcohol dependence. METHODS: We compared allele frequencies of five HTR2C promoter polymorphisms in a Nordic population of alcohol dependent individuals (Males: n = 309; Females: n = 127) and ethnically matched controls (Males: n = 83; Females: n = 190) in whom alcohol dependence was established, or any diagnosis of substance disorder was excluded, respectively. Patients were further subtyped into Type I (late onset) and Type II (early onset) alcoholics. RESULTS: None of the individual polymorphisms indicated significant association with alcohol dependence. A common promoter haplotype (GAGG) exhibited different distribution frequencies between males and females (Type I), however on Bonferroni's multiple-testing correction, this observation proved to be insignificant. CONCLUSIONS: Although we report a lack of association between alcohol dependence and five common promoter polymorphisms, and the constituted haplotypes, the analysis tends to indicate gender and sub-type differences. We suggest that a follow up study with larger sample numbers should be performed to improve the power to detect the genetic influences of HTR2C in alcohol dependence.
Three genes mutations in which cause familial forms of Alzheimer's disease are known to date:PSEN1, PSEN2 and APP; and APOE gene polymorphism is a strong risk factor for Alzheimer's disease. We have evaluated allele and genotype frequency distribution of rs11136000 polymorphism in clusterin (CLU) gene (or apolipoprotein J, APOJ) in populations of three Russian regions and i nAlzheimhner's diseasepatients. Genome-wideassociation studies in samples from several European populations have recently revealed highly significant association o fCLU gene with AD (p = 8.5 x 10(-10)). We found no differences in allele and genotype frequencies of rs11136000 between populations from Moscow, Ural and Siberia regions. The allele frequencies are close to those in European populations. The genetic association analysis in cohort of Alzheimer's disease patients and normal individuals (>500 individuals ineach group) revealed no significant association of the rs11136000 polymorphism in CLU with Alzheimer's disease in Russian populations. Although our resultsdo not confirm the role of CLU gene as a majorgenetic factor forcommon form of Alzheimer's disease, the data do not rule out the possibility of modest effect of CLU and interaction between CLU and APOE genotypes in etiology of Alzheimer's disease.