Interleukin-21 gene polymorphisms and chronic hepatitis B infection in a Chinese population.

AIM: To investigate the relationship between interleukin-21 (IL21) gene polymorphisms and chronic hepatitis B virus (HBV) infection in a Chinese population. METHODS: In this case-control study, 366 Chinese HBV-infected patients were recruited and divided into hepatocellular carcinoma (HCC; n = 94) and non-HCC (n = 272) groups at The First Affiliated Hospital of Sun Yat-Sen University, from April 2009 to December 2012. In the non-HCC group, the patients were classified into three clinical subsets, 76 patients had chronic hepatitis B, 101 were HBV carriers and 95 patients had HBV-related cirrhosis. Two hundred eight unrelated healthy controls were also included. Genomic DNA was extracted from peripheral blood. Single nucleotide polymorphisms (SNPs) rs13143866, rs2221903, and rs907715 were subsequently genotyped using the SNaPshot SNP technique. RESULTS: There were no significant differences in allele and genotype frequencies of SNPs rs13143866, rs2221903, and rs907715 between chronic HBV-infected patients and control subjects. Furthermore, no significant differences were found in the frequencies of all alleles and genotypes between the HCC group and the non-HCC group. However, in the subgroup analysis, IL21 rs13143866 genotype AA frequency in the HBV carrier group was higher than in controls (OR = 6.280, 95%CI: 1.238-31.854; P = 0.019), and the effect of the recessive model (AA vs GG + GA, OR = 6.505, 95%CI: 1.289-32.828) was observed in the HBV carrier group. IL21 rs2221903 genotype TC frequency in the HBV carrier group was higher than in controls (OR = 1.809, 95%CI: 1.043-3.139; P = 0.035). In the haplotype analysis, the ATA haplotype (rs13143866, rs2221903, and rs907715) of IL21 was more frequent in the HCC group than in the non-HCC group (0.165 vs 0.104, P = 0.044; OR = 1.700, 95%CI: 1.010-2.863). CONCLUSION: Genotypes rs13143866 AA and rs2221903 TC are risk factors for carrying HBV; ATA haplotype increases the risk of HBV-related HCC onset in a Chinese population.

Apolipoprotein C3 (-455T>C) polymorphism confers susceptibility to nonalcoholic fatty liver disease in the Southern Han Chinese population.

AIM: To investigate the relationship between Apolipoprotein C3 (APOC3) (-455T>C) polymorphism and nonalcoholic fatty liver disease (NAFLD) in the Southern Chinese Han population. METHODS: In this prospective case-control study, we recruited 300 NAFLD patients and 300 healthy controls to a cohort representing Southern Chinese Han population at The First Affiliated Hospital, Sun Yat-sen University, from January to December 2012. Polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing were used to genotype the APOC3 (-455T>C) variants. RESULTS: After adjusting for age, gender, and body-mass index, TC and CC genotypes were found to increase the susceptibility to NAFLD compared to the TT genotype, with adjusted odds ratios (ORs) of 1.77 (95%CI: 1.16-2.72) and 2.80 (95%CI: 1.64-4.79), respectively. Further stratification analysis indicated that carriers of the CC genotype was more susceptible to insulin resistance (IR) than those of the TT genotype, with an OR of 3.24 (95%CI: 1.52-6.92). The CC genotype also was associated with a significantly higher risk of hypertension, hypertriglyceridemia, and low levels of high-density lipoprotein cholesterol (HDL) (P < 0.05). No association was found between the APOC3 (-455T>C) polymorphism and obesity, impaired glucose tolerance, hyperuricemia, hypercholesterolemia, or high levels of low-density lipoprotein cholesterol (LDL) (P > 0.05). CONCLUSION: APOC3 (-455T>C) genetic variation is involved in the susceptibility to developing NAFLD, IR, hypertension, hypertriglyceridemia, and low HDL in the Southern Chinese Han population.

[Imbalance of CD4(+) T cell subgroups in ulcerative colitis].

OBJECTIVE: To investigate the relationship of the imbalance of CD4(+) T cell subgroups and the pathogenesis of ulcerative colitis (UC). METHODS: Peripheral blood samples were collected from 24 UC patients and 17 healthy donors. Then the phenotype of CD4(+) T cells and the major transcription factor expression of each subset were analyzed by flow cytometry and real-time PCR (polymerase chain reaction) respectively. The serum concentrations of major cytokines of each subgroup were measured by cytometric bead array (CBA) and ELISA (enzyme-linked immunosorbent assay). RESULTS: (1) The proportion of Treg cells in the UC group was lower than the control group (6.7% ± 1.7% vs 7.9% ± 1.4%, P = 0.016), especially in active stage (6.4% ± 1.7%, P = 0.005). As compared with the control group, the expression of FOXP3 mRNA was lower in the UC Group (P = 0.020). And so was the serum concentration of TGF-ß1 [(21 ± 8) µg/L vs (28 ± 7) µg/L, P = 0.026]. (2) There were no significant differences in Th1-related transcription factors and cytokines between two groups. (3) Th2 cells were higher in the UC group (2.7% ± 1.1% vs 1.6% ± 0.4%, P = 0.002), especially in active stage (2.8% ± 1.0%, P = 0.001). The expression of GATA-3 mRNA was 4.4 folds higher than that of the controls (P = 0.045). (4) Th17 cells were higher in the UC group (3.4% ± 1.8% vs 1.8% ± 0.7%, P = 0.005). And the RORγt mRNA expression was 13 folds higher in UC group (P = 0.001); the serum concentrations of IL-6 and IL-17 were higher in the UC group (both P < 0.05). (5) The ratios of Treg/Th2 and Treg/Th17 were significantly lower in the UC group and associated with disease activity (both P < 0.05). CONCLUSION: The imbalances of Th2, Treg and Th17 subgroups may play pivotal roles in the pathogenesis of UC.