Evaluation of death pathway genes FAS and FASL polymorphisms in chronic HBV infection.

This study was designed to determine the possible asssociation between selected FAS and FASLG polymorphisms and Hepatitis B virus (HBV) infection. FAS-670 G/A, FAS-1377 G/A, FASLG-844 T/C and FASLG IVS2nt-124 A/G polymorphisms were genotyped by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). A total of age and sex matched 108 controls and a hundred chronic HBV patients were recruited to conduct a case-control study. FAS-670 polymorphism was associated with chronic HBV infection (P = 0.03) FAS-1377 GG, GA and AA genotypes among the cases (90%, 5% and 5%, respectively) were significantly different from those among the controls (68%, 31.5% and 5.6%; P = 0.00). FASLG-844 allele distribution was similar between the groups (P = 0.17) but TC genotype (67.3%) was frequent in chronic HBV patients, while CC genotype was found significantly higher (29.6%) in controls. No association between FASLG IVS2nt-124 polymorphism and chronic HBV infection could be identified (P = 0.55). FAS-670 polymorphism is associated with chronic HBV infection, while FASLG IVS2nt-124 A/G polymorphism is not. The FAS-1377G/A and FASLG-844 T/C genotypes are likely to play a substantial role in HBV infection. Further studies evaluating polymorphisms in other genes related with apoptosis are needed to elucidate the role of genetic variation in HBV infection.

Association between dopamine beta hydroxylase gene polymorphism and age at onset in male schizophrenia.

OBJECTIVES: The heterogeneity of schizophrenia mainly results from variations in clinical expressions of the disease, such as age at onset, gender differences in onset of illness, symptoms and response to antipsychotic treatment. Enhanced sensitisation of dopamine pathways in males, having consistently an earlier onset, might be implicated as disease modifiers for schizophrenia in males. METHODS: In this study, we performed a case (n = 87)-control (n = 100) association study between the DBH5'-ins/del and DBH-444g/a polymorphisms of the DBH gene and also compared the level of psychotic symptoms between patients with different DBH genotypes/haplotypes with respect to antipsychotic therapeutic response and gender difference. RESULTS: No significant differences between allele and genotype and haplotype frequencies at either groups (p < 0.05). When the age is considered in patient group, a significant difference was observed between patients with ID genotype and with II genotype (p = 0.018). Patients with ID genotype have been diagnosed as schizophrenics in early ages when compared to II genotype carriers. We also found a significant difference between II and ID genotype (p = 0.007) when the gender had taken into account, showing that the ID genotype carriers had an early onset to schizophrenia. CONCLUSIONS: This association was more significant in male schizophrenia patients than females. Thus, this finding may constitute a novel biological support for the prior finding that onset of schizophrenia varies with gender. The results also showed that critical genetic vulnerability may be associated with the presence or absence of the ID genotype of DBH5'-ins/del.

Tumour necrosis factor alpha -308G/A gene polymorphism: lack of association with knee osteoarthritis in a Turkish population.

OBJECTIVE: To study the association between TNFalpha-308 G/A polymorphism and susceptibility to and severity of knee osteoarthritis in a Turkish population. METHODS: Genomic DNA was obtained from 151 patients with knee osteoarthritis and 84 ethnically matched healthy controls. Polymerase chain reaction-restriction fragment length analysis was used to identify G/A polymorphism at position -308 in the promoter region. Genotype distributions and allelic frequencies of TNFalpha-308 G/A polymorphism were compared between osteoarthritis patients and controls. Thereafter, this association was investigated between patients and controls of the same sex. In addition, the standard Kellgren-Lawrence grading score and the Turkish version of the Western Ontario and McMaster Universities Osteoarthritis Index were used to assess the radiological and functional severity of the disease and their relationship with the TNFalpha-308 gene polymorphism was investigated. RESULTS: Genotype distribution and allelic frequencies of -308 G/A polymorphism in the TNFalpha gene did not differ significantly between patients with knee osteoarthritis and controls (p>0.05). Moreover, there were no significant differences between patients and controls of the same sex (p>0.05). In addition, no association was observed between the radiological and functional severity of the disease and TNFalpha-308 G/A polymorphism (p>0.05). CONCLUSION: These findings suggest that the examined polymorphism in the TNFalpha gene does not contribute to susceptibility to or severity of knee osteoarthritis in the Turkish population.