[A study of the association of iNOS and eNOS gene polymorphism with portal hypertension in liver cirrhosis].

OBJECTIVE: To study whether polymorphism of iNOS and eNOS genes is associated with portal hypertension in liver cirrhosis. METHODS: A case control study of 106 patients with liver cirrhosis due to HBV was performed in comparison with 108 controls using PCR-RFLP to detect iNOS promoter -969G --> C and eNOS exon7 894G --> T polymorphism. RESULTS: The frequency of the C allele and GC genotype in the iNOS promoter -969G --> C was significantly higher in the portal hypertension group than in the control group. (P < 0.05). The frequency of the T allele and GT genotype in eNOS exon7 894G --> T was dramatically higher in the portal hypertension group than in the control group (P < 0.05). Multivariate logistic regression analysis revealed that iNOS polymorphism in iNOS promoter -969G --> C and eNOS exon7 894G --> T was an independent new risk factor for portal hypertension. We discovered that iNOS promoter -969G --> C led to an increase in its functional activity. CONCLUSIONS: The polymorphism of iNOS promoter -969G --> C and eNOS exon7 894G --> T is associated with portal hypertension of liver cirrhosis, which is a new independent risk factor found related to the occurrence of portal hypertension. The polymorphism of iNOS promoter -969G --> C results in functional activity increase of the iNOS promoter.

[Polymorphism of NOS2A promoter -969(G>C) is associated with portal hypertension of liver cirrhosis].

OBJECTIVE: To determine whether polymorphism of NOS2A promoter -969G>C is associated with the portal hypertension of liver cirrhosis. METHODS: A case control study covering 106 patients with liver cirrhosis due to hepatitis B virus(HBV) in comparison with 108 controls was performed using PCR-restriction fragment length polymorphism. The NOS2A mRNA and protein expression in liver cirrhosis tissues were detected by reverse transcription-PCR and Western blot. The recombinant plasmids of NOS2A promoter luciferase reporter gene were constructed and were transfected transiently into HepG2 cells for analyzing the functional activity of the promoter. RESULTS: The frequencies of the C allele and GC genotype at NOS2A promoter -969G>C were significantly higher in portal hypertension group (16.9%, 33.8%) than in control group(8.8%, 17.6%)(P<0.05), and positive correlation (r=0.18) and association (OR=2.42) were noted. There was no significant difference in frequency distribution between single liver cirrhosis group and control group(P>0.05). The expressions of NOS2A mRNA and protein in liver cirrhosis tissues were more increased in C allele carriers with liver cirrhosis than in G allele carriers with liver cirrhosis, which led to higher functional activity of the promoter. Multivariate logistic regression analysis revealed that NOS2A polymorphism at promoter -969G>C is an independent novel risk factor for the occurrence of portal hypertension in patients with liver cirrhosis. CONCLUSION: The polymorphism of NOS2A promoter -969(G>C) is associated with portal hypertension of liver cirrhosis, which results in functional activity increase of NOS2A promoter and is an independent risk factor for portal hypertension.

[Relationship of endothelin-1 (ET-1) TaqI and tumor necrosis factor (TNF) a gene polymorphism with portal hypertension in liver cirrhosis].

OBJECTIVE: To study whether liver cirrhosis and portal hypertension are associated with ET-1 TaqI polymorphism and TNFa promoter-308G to A polymorphism. METHODS: A case control study of 106 patients with liver cirrhosis following HBV C infection was performed in comparison with 108 controls by PCR-RFLP. RESULTS: The frequency of C allele and CC+TC genotype in TaqI polymorphism of ET-1 gene in the portal hypertension group (LC+) was significantly higher than that in the healthy controls, and the frequency of TNF2/1 genotype in TNFa promoter -308 G to A polymorphism in LC+ group was significantly higher than that in the control group. The results by stratification analysis showed that TCF2 genotype frequency was higher in the LC+ group than in the control group. ET-1 TaqI polymorphism and TNFa polymorphism were risk factors for the occurrence of portal hypertension by Logistic regression analysis. CONCLUSION: ET-1 TaqI polymorphism and TNFa polymorphism are associated with portal hypertension, and are new risk factors for the occurrence of portal hypertension. TCF2 genotype may be a susceptible gene of portal hypertension.

[The association between polymorphism of endothelial nitric oxide synthase gene and cirrhotic portal hypertension].

OBJECTIVE: To study whether the liver cirrhosis and portal hypertension are associated with a -786T-->C mutation at promoter and VNTR polymorphism in intron 4 and a 894 G-->T mutation at exon 7 of the eNOS. METHODS: A case control study of 106 patients with liver cirrhosis due to HBV was performed in comparison with 108 controls with the help of PCR-SSCP or RFLP. RESULTS: There was no difference in the gene frequency of allele G of promoter between LC(+) group and other groups. The frequencies of the T and TG genotype at exon7 and the a allele and ab genotype in intron 4 were significantly higher in portal hypertension group (LC(+)) than in liver cirrhosis group alone and control group (P < 0.05). Patients of the liver cirrhosis with coexistence of the T and a alleles had a higher incidence of portal hypertension (P < 0.05) than those with only one of the two alleles or without any of the two alleles. Multivariate logistic regression analysis revealed that VNTR polymorphism in intron 4 and 894 G-->T mutation at exon 7 of the eNOS gene are independent risk factors for the occurrence of portal hypertension in patients with liver cirrhosis. CONCLUSION: The T allele at exon 7 and a allele in intron 4 are associated with the occurrence of portal hypertension in patients with liver cirrhosis. The ocurrence of portal hypertension with liver cirrhosis is higher in patients who have both T and a allele than patients who have either T or a allele alone, which is an independent risk in occurrence of portal hypertension, respectively. TGab may be susceptibility genotype of portal hypertension.

[Correlation between polymorphism of TaqI of ET-1 gene and cirrhotic portal hypertension].

OBJECTIVE: To investigate the correlation between polymorphism of TaqI of endothelin (ET)-1 gene intron 4 and cirrhotic portal hypertension and to search new risk factor of portal hypertension. METHODS: Peripheral venous blood was extracted from 106 patients with cirrhosis after hepatitis B (PH+ group) and 108 healthy blood donors (PH- group). PCR-RFLP was used to analyze the polymorphism of TaqI of ET-1 gene. The plasma ET-1 concentration was detected with immunoassay. Multivariate logistic regression analysis was made to analyze the risk factors. RESULTS: The C allele frequency in the PH+ group was 25.4%, significantly higher than that of the controls (16.7%, P < 0.05). The frequency of CC + TC genotype in PH+ group was 46.2%, significantly lower than that in the controls (29.6%, P < 0.05). In the PH+ group, the thickness of spleen was greater, hemorrhage rate was higher, and III degrees ascites was more in C allele carrier than in T allele carriers (P < 0.05). The plasma ET-1 concentration was higher in PH+ group than in PH- group. In the PH+ group, the plasma ET-1 concentrations in those with CC genotype and those with TC genotype were significantly higher than in those with TT genotype (P < 0.05). Correlation analysis showed that ET-1 gene polymorphism was positively correlated with plasma ET-1 concentration (R = 0.808 2). Multivariate logistic regression analysis showed that gradation of liver function, diameter of portal vein, and ET-1 gene polymorphism were independent risk factors of portal hypertension. CONCLUSION: Polymorphism of TaqI of ET-1 gene is correlated with the pathogenesis of cirrhotic portal hypertension. It may be one of the risk factors of portal hypertension.

[The association of HLA-DRB1 allele polymorphism with the genetic susceptibility to liver cirrhosis due to hepatitis B virus].

OBJECTIVE: To assess the association of human leucocyte antigen (HLA)-DRB1 allele with the genetic susceptibility to cirrhosis due to hepatitis B virus(HBV). METHODS: One hundred and six patients with cirrhosis due to HBV in Hubei area were investigated for HLA-DRB1 gene by polymerase chain reaction-sequence specific primers technique. The results were compared with those from 108 normal healthy people. RESULTS: The frequency of HLA-DRB1*1201/1202 allele was 20.28% in patient group, which was significantly higher than the frequency (6.01%) in control group, the relative risk (RR) being 4.9878 (P<0.01). The frequency of HLA-DRB1*1501/1502 allele was decreased in patient group (patient 6.6%, control 16.67%, RR=0.3043, P<0.05), while the frequencies of other HLA-DRB1 alleles were not significantly different(P>0.05). CONCLUSION: HLA-DRB1*1201/1202 allele may be the susceptibility gene in patients with cirrhosis due to HBV in Hubei Han nationality; HLA-DRB1*1501/1502 allele is a resistant gene in patients with cirrhosis.

[Tumor necrosis factor alpha HLA-DRB(1) gene polymorphism and genetic susceptibility to cirrhosis].

OBJECTIVE: To study the relationship between the gene polymorphism of HLA-DRB(1) and tumor necrosis factor (TNF)alpha with the genetic susceptibility to cirrhosis. METHODS: The gene polymorphism of DRB(1) and TNF alpha of 106 cases of cirrhosis due to HBV and 108 controls were detected by means of polymerase chain reaction-sequence specific primer and RFLP techniques. RESULTS: The frequency of DRB(1) * 120X and TNF2/1 was increased in the patients as compared with the controls (35.9% vs 11.1%, P < 0.001, 19.8% vs 10.2%, P < 0.05 respectively), The frequency of DRB(1) * 150X allele was reduced in the patients as compared with the controls (13.2% vs 30.6%, P < 0.05). It is suggested that the gene polymorphism of HLA-DRB(1) and TNF alpha to be associated with genetic susceptibility to cirrhosis. Cross analysis showed that DRB(1) * 120X allele was more strongly associated with genetic susceptibility to cirrhosis than TNF2 allele. CONCLUSIONS: The genetic susceptibility to cirrhosis is associated with DRB(1) * 120X and TNF2 allele, persons with DRB(1) * 120X and TNF2 allele have an increased risk for the liver cirrhosis occurrence; DRB(1) * 120X allele may be a susceptibility gene to liver cirrhosis and DRB(1) * 150X allele may be a protective gene from liver cirrhosis.