Search NEL Online

Journal Article 2013; 34(5): 402-408 PubMed PMID: 23922043 Citation  Keywords:  Adult, Alleles, Antigens, Differentiation, T-Lymphocyte:genetics, Asian Continental Ancestry Group:genetics, Female, Gene Frequency, Genetic Association Studies, Genetic Predisposition to Disease, Genotype, Humans, Linkage Disequilibrium, Male, Middle Age.   

OBJECTIVE: This study was conducted to find the possible association between CD226 polymorphisms and inflammatory demyelinating diseases in Korean population.

METHODS: A total of 14 CD226 SNPs were selected based on their linkage disequilibrium, minor allele frequency, and location. Then, the SNPs were genotyped in 178 IDD patients and 237 healthy controls. Subsequently, we conducted logistic analysis to find possible associations

RESULTS: Statistical analyses revealed only a marginal signal for a common SNP rs1788229 with inflammatory demyelinating disease (p=0.05), while other SNPs failed to show associations with any diseases. However, the significance of rs1788229 disappeared after a multiple testing correction of the data (p>0.05). Interestingly, rs763361, which showed significant associations with multiple sclerosis in several previous studies, did not show any association at all.

CONCLUSIONS: While prior studies have found CD226 polymorphisms to be significantly associated with inflammatory demyelinating diseases, our results indicate the CD226 polymorphisms to be not associated with the diseases in Korean population. However, our results suggest that the causal genes for inflammatory demyelinating diseases may vary depending on the population....

Read abstract  Full text PDF

Journal Article 2012; 33(2): 236-244 PubMed PMID: 22592207 Citation  Keywords:  Adolescent, Adult, Aged, Alleles, Antipsychotic Agents:adverse effects, Cytochrome P-450 CYP2D6:genetics, Female, Genotype, Humans, Male, Middle Aged, Prospective Studies, Psychiatric Status Rating Scales:statistics & numerical data, Psychotic Disorders:d.   

OBJECTIVE: The objective of this prospective, naturalistic study, conducted in first-episode psychosis patients from a Central-European population, was to assess the utility of Cytochrome P-450 2D6 (CYP2D6) genotype testing under normal clinical setting.

METHODS: A total of 35 patients diagnosed for the first time with schizophrenia or acute schizophrenia-like psychotic disorder and treated with risperidone were enrolled in the study. These patients underwent sequentiation of the CYP2D6 gene and evaluations of symptoms and severity of adverse effects using the PANSS and UKU scales, respectively. Doses of antipsychotics and other co-medication were monitored as well. In statistical analysis, Fisher's exact test was used to compare ratios and the Wilcoxon rank-sum test was used in the comparison of continual variables.

RESULTS: PM patients showed a significantly lower reduction in psychotic symptoms and a greater severity of psychotic symptoms following risperidone treatment and higher doses of antipsychotics not metabolized by CYP2D6, which were used as co-medication.

CONCLUSIONS: Based on these results, patients with the PM genotype experiencing first-episode schizophrenia don't appear to be optimal recipients of risperidone treatment. However, as the main limitation of this study was the relatively small sample-size, replication with a larger scale study is needed to confirm these findings....

Read abstract  Full text PDF

Journal Article 2010; 31(4): 549-552 PubMed PMID: 20802447 Citation  Keywords:  Aged, Aged, 80 and over, Alleles, Czech Republic, Essential Tremor:genetics, Female, Gene Frequency, Genetic Association Studies, Genetic Heterogeneity, Genetic Loci, Genetic Predisposition to Disease, Genotype, Haplotypes, Humans, Male, Microsatellite Re.   

OBJECTIVES: Essential tremor (ET) is one of the most common neurological movement disorders. In more than half of the cases, ET is inherited in an autosomal dominant manner, but no causative ET gene has been identified. However, several candidate loci have been reported, including the ETM2 locus that was originally found in a large American family of Czech descent.

METHODS: To ascertain the association with ETM2, we performed a genetic analysis of three polymorphic loci, etm1231, etm1234, and etm1240, located within the ETM2 candidate region in 61 Czech patients with a family history of ET and 68 healthy controls.

RESULTS: The allele frequencies were not significantly different between the patients and the controls, and we did not observe any haplotype specifically associated with ET.

CONCLUSIONS: This is the first report on the genetics of familial essential tremor in Czech patients. Our findings provide further evidence of genetic heterogeneity for ET....

Read abstract  Full text PDF

Journal Article 2009; 30(Suppl 1): 137-142 PubMed PMID: 20027160 Citation  Keywords:  Adult, Alleles, Azathioprine:adverse effects, Female, Genetic Predisposition to Disease, Genotype, Humans, Leukopenia:chemically induced, Male, Methyltransferases:genetics, Polymerase Chain Reaction, Polymorphism, Genetic, Polymorphism, Single Nucleotide,.   

OBJECTIVES: Our study aims to find the relationship between metabolic enzyme thiopurine S-methyltransferase (TPMT) gene polymorphisms and clinical output of the therapy with azathioprine. We focused on patients who experienced leucopenia caused by high blood levels of active azathioprine metabolites.

DESIGN: Our group consists of 87 patients who have been treated by azathioprine. 21 individuals experienced leucopenia during treatment with standard dose of azathioprine. We have used PCR-REA and "real-time" PCR methods for genotype detection G238C, G460G and A719G substitutions in TPMT gene.

RESULTS: We have found statistical association between the presence of non-standard TPMT alleles and adverse event associated with azathioprine treatment - leucopenia (p=0.0033).

CONCLUSION: Our results confirm that TPMT genotyping prior to the treatment with azathioprine could predict patients with genetic predisposition for serious leucopenia and seems to be a useful genetic marker for individualisation of the therapy....

Read abstract  Full text PDF

Journal Article 2009; 30(3): 357-362 PubMed PMID: 19855359 Citation  Keywords:  Adult, Alleles, Catalase:genetics, Chi-Square Distribution, Depressive Disorder:genetics, European Continental Ancestry Group:genetics, Female, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Male, Oxidative Stress:genetics, Patient S.   

: Numerous studies have provided information indicating the involvement of oxidative stress in the pathophysiology of depressive disorder (DD). The antioxidative system protects against the effects caused by reactive oxygen species (ROS). Catalase (CAT) is one of antioxidative enzymes observed to change their levels in the course of depression. The enzyme decomposes hydrogen peroxide (H(2)O(2)), whose overproduction is a result of many processes taking place in depression. Therefore, functional polymorphism of the CAT gene can be a candidate marker of the risk of depression. The presented study assessed the correlation between -262C>T polymorphism of the CAT gene, which influences the increase of CAT expression and activity, and the risk of depression development. The study, carried out on a homogeneous group recruited from the Polish population, enrolled 149 healthy subjects and 149 depressive patients. The groups were age-matched. The obtained results indicate no correlation between -262C>T polymorphism of the CAT gene (both with respect to genotype distribution and allele frequency) and the risk of depression. Nevertheless, further studies assessing the correlations between depression and polymorphism of the genes encoding antioxidative enzymes on larger groups of subjects should be undertaken....

Read abstract  Full text PDF

Journal Article 2008; 29(3): 334-340 PubMed PMID: 18580850 Citation  Keywords:  Adolescent, Alleles, Antigens, CD:genetics, Autoimmune Diseases:epidemiology, CTLA-4 Antigen, Celiac Disease:epidemiology, Child, Cohort Studies, Diabetes Mellitus, Type 1:epidemiology, Endocrine System Diseases:epidemiology, Female, Genetic Markers, Geno.   

OBJECTIVES: The aim of the study was to determine the association of two CTLA-4 gene polymorphisms (CT60, +49 A/G) with Hashimoto thyroiditis (HT), type 1 diabetes mellitus (T1DM) and celiac disease (CD) as well as with the occurrence of multi-organ involvement by autoimmunity in children.

METHODS: Genotyping was done by RFLP analysis in Slovak children with HT (n=63) and CD (n=120) and both Slovak and Slovene children with T1DM (n=320) and healthy controls (n=231).

RESULTS: We found a significant association of the G allele of the CT60 polymorphism with HT (p<0,0005) in the Slovak population and T1DM in both Slovak (p<0.01) and Slovene populations (p<0.005). The G allele of the +49A/G polymorphism was significantly, though less strongly, associated with T1DM (p<0.05) and HT (p<0.05). Distribution of genotypes of CTLA-4 gene polymorphisms in CD patients did not differ significantly from controls. None of the polymorphisms was associated with multi-organ involvement by autoimmunity.

CONCLUSION: The G allele of both examined CTLA-4 gene polymorphisms predisposes to HT and T1DM, but not to CD. No association with multi-organ involvement was found. The GG genotype of the CT60 polymorphism may identify CD patients at an increased risk for concomitant T1DM and HT. Further studies to assess the predictive value of CTLA-4 polymorphisms for the co-occurrence of HT and T1DM in CD patients are needed....

Read abstract  Full text PDF

Journal Article 2006; 27(1-2): 219-224 PubMed PMID: 16648810 Citation  Keywords:  3-Hydroxysteroid Dehydrogenases:genetics, Adrenal Cortex Hormones:metabolism, Alleles, Child, China:epidemiology, Female, Gene Frequency, Genotype, Gonadal Steroid Hormones:blood, Humans, Insulin Receptor Substrate Proteins, Molecular Sequence Data, Phosp.   

OBJECTIVES: In order to investigate whether the variances in the candidate genes (Insulin receptor substrate IRS-1, beta3-adrenergic receptor ADRB3, 3 beta-hydro-xysteroid dehydrogenase HSD3B2, glucocorticoid receptor GRL and 21-hydroxylase CYP21) which affect the metabolism of adrenal steroids hormone and body composition, are associated with precocious puberty in Chinese girls.

METHODS: PCR-RFLP analysis method was applied in the typing of six activity SNPs in five genes in two groups: 176 precocious puberty girls as case and 192 healthy girls as control.

RESULTS: The typing results showed that the frequencies of the allele CYP21 L282 polymorphism were 32.7% and 32.6% in case and control groups (P=0.518), respectively. For IRS-1 R972, they were 0.6% in cases and 2.3% in controls (P=0.043), for ADRB3 R64, 13.6% in cases and 12% in controls (P=0. 378), and for GRL S363, 7.4% in cases and 5.73% in controls (P=0.335). No sample in the two groups carries the variation of CYP21 I172N and HSD3B2 L236S.

CONCLUSION: Among these six activity SNPs in five candidate genes, IRS-1 972R was statistically associated with the onset time of puberty in Chinese girls. In order to confirm whether the candidate genes have any other activity SNPs that are associated with the onset time of puberty in Chinese girls, resequencing of these candidate genes is needed in following time....

Read abstract

Journal Article 2006; 27(1-2): 236-240 PubMed PMID: 16648784 Citation  Keywords:  Adolescent, Alleles, Attention Deficit Disorder with Hyperactivity:epidemiology, Child, Czech Republic:epidemiology, DNA:genetics, Gene Frequency, Humans, Male, Polymorphism, Genetic, Psychiatric Status Rating Scales, Receptors, Dopamine D2:genetics, Reve.   

OBJECTIVES: Attention deficit hyperactivity disorder (ADHD) is a prevalent childhood disorder. Evidence from the family and twin studies suggest that ADHD is familiar and highly heritable. Association studies are frequently used for the searching of markers responsible for genetic basis of ADHD. We investigated TaqI polymorphism of the dopamine receptor D2 (DRD2) in relationship with ADHD. The association between TaqI A polymorphism of DRD2 gene and ADHD has previously been published.

DESIGN: We used the association study to test the relationship between TaqI A polymorphism of DRD2 gene and ADHD on groups of ADHD boys and control boys.

SETTING: For DNA isolation, buccal tissue was used. PCR with restriction analysis of PCR products was used for genotyping.

RESULTS: We found statistically different genotypic and allelic frequencies (p < 0.008, p < 0.002, respectively) of DRD2 polymorphism between two studied groups of boys.

MAIN FINDINGS: According to our results we suppose that polymorphism TaqI A of DRD2 gene is involved in the pathogenesis of childhood ADHD in male subjects. Allele A1 and genotype A1A1 in male subjects is associated with ADHD.

CONCLUSIONS: Our study confirmed the relationship between TaqI A polymorphism of DRD2 gene and ADHD published previously....

Read abstract