| A pharmacogenetic study of response to a interferon treatment in chronic hepatitis B patientsBackgroundsChronic hepatitis B (CHB) is the heavy burden of economy, society and health problem in China, with 120 millions to 150 millions Hepatitis B Virus (HBV) carriers and the annual medical cost related to hepatitis B reaches 30 billion RMB. Interferon a (IFNa) is one of the first line drugs against HBV. However, variation of response to IFNa between individuals is the main problem that interferes with the clinical treatment. In this present study, nested case control study was used to perform the pharmacogenetic study of IFNa against HBV, with adenosine deaminase (ADAR) gene, interferon a receptor 1 (IFNAR1) gene, Janus kinase 1 (JAK1) gene, and 2',5'-oligoadenylate synthetase (OAS) gene as the candidate genes.MethodsTwo hundred and forty-six IFNa treatment-naive CHB patients were enrolled for the present study; all received treatment with IFNa alone for 6 months, and the efficacy of the therapy was examined. Twelve single nucleotide polymorphisms (SNP), namely rs3738032, rs1127314, rs3766924 in ADAR gene, rs2252930 in IFNAR1 gene, rs17127090, rs2780895, rs4244165, rs17127024 in JAK1 gene, rs3177979, rs1293747, rs4767043, rs10849829 in OAS gene family were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) protocol. Statistical analyses were performed using the SPSS statistical package, version 12.0. The haplotype estimation was carried out using the SHEsis online software.ResultsAfter 6 months of therapy, we evaluated the efficacy of IFNa in the 246 patients on the basis of the criteria for combined assessment. The response rate was 68.7%(169/246), with 16.3%of the patients showing complete response (40/246) and 52.4%showing partial response (129/246). There was no significant difference in the distribution of age and gender among the 3 groups, but the mean levels of ALT in the complete response and partial response groups were both higher than that in the non-response group (189.0 IU/L in CR,156.5 IU/L in PR, and 100.3 IU/L in NR, P=0.001). There were no significant differences in allele frequencies and genotype distributions of the 12 SNPs studied between the response and non-response groups. However, the frequency of a GCTG JAK1 haplotype was significantly higher in the non-response group than that in the response group (11.9%vs.5.6%, P=0.016, OR=2.25,95%CI=1.15-4.40). And the frequency of a GTGA OAS haplotype was also significantly higher in the non-response group than that in the response group (16.1%vs.8.7%,P=0.015, OR=2.01, 95%CI=1.13-3.58).ConclusionsOur study suggested that patients with lower mean levels of ALT, a GCTG JAK1 haplotype and a GTGA OAS haplotype were less responsive to IFNαtreatment. The association studies of polymorphisms in the ApoM gene and KIAA0350 gene with type 1 diabetesBackgroundsType 1 diabetes (TID) is an autoimmune disease, which is mainly caused by the destruction of the insulin-producingβcells of the pancreas. The prevalence of TID varies according to different ethnicities and regions in the world. The prevalence of TID is high in Sweden (the overall age-adjusted incidence is about 27.5/100,000 per year), but low in China (about 0.1/100,000 per year). TID is a complex disease, and both genetic and environmental factors contribute to its etiology. In the present study, we performed genetic association study of three ApoM promoter polymorphisms and two KIAA0350 polymorphisms in two TID populations. Furthermore, we have analyzed the influences of the polymorphisms on the ApoM promoter activity.MethodsTID patients and non-diabetic control subjects in Han Chinese or Swedish population were recruited in this study. Five polymorphisms of 2 candidate genes were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) protocol. Statistical analyses were performed using the SPSS statistical package, version 12.0. The haplotype estimation was carried out using the PHASE program (version 2.1) or the SHEsis online software. The plasmids of different alleles in the promoter of ApoM gene were constructed with pGL3-Basic vector. Dual-luciferase(?) reporter assay system was used to detect the transcriptional activities.Results1. Association of polymorphisms in ApoM gene with T1DTwo populations, including 493 Han Chinese subj ects (177 T1D patients/316 controls) and 225 Swedish (124/101), are enrolled in the present study. Three single nucleotide polymorphisms (SNP) C-1065 A, T-855C and T-778C in the promoter region of the ApoM gene were genotyped. SNP T-778C was strongly associated with TID in both Han Chinese (P=0.002, OR=2.188, CI95%=1.338-3.581) and Swedish (P=0.021, OR=2.865, CI95%=1.128-7.278) populations. The luciferase activity of-778C promoter was 1.41 times as high as that of-778T promoter (P= 0.001).2. Association of polymorphisms in KIAA0350 gene with T1DA total of 205 TID patients and 422 non-diabetic subjects of the Han Chinese population were enrolled. Two SNPs, namely, rs17802927 and rs725613, in the KIAA0350 gene were genotyped. The intron SNP rs725613 was strongly associated with TID in the Han Chinese population (P=0.00007, OR=0.527,95%CI=0.383-0.726). Four haplotypes were constructed using these two SNPs. The frequency of the G-T haplotype was significantly higher in the TID patients than in the ND controls (7.8%vs.1.8%, P= 2.52×10-7). The frequency of the A-G haplotype was significantly lower in the TID patients than in the ND controls (9.3%vs.16.2%, P=0.00068).ConclusionsSNP T-778C in the promoter region of the ApoM gene may influence promoter activity and the susceptibility to development of T1D in both Han Chinese and Swedish population. The intron polymorphism rs725613 in the KIAA0350 gene is associated with susceptibility to T1D in Han Chinese population.
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