A study of the association of iNOS and eNOS gene polymorphism with portal hypertension in liver cirrhosis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study whether polymorphism of iNOS and eNOS genes is associated with portal hypertension in liver cirrhosis.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Relationship of endothelin-1 (ET-1) TaqI and tumor necrosis factor (TNF) a gene polymorphism with portal hypertension in liver cirrhosis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study whether liver cirrhosis and portal hypertension are associated with ET-1 TaqI polymorphism and TNFa promoter-308G to A polymorphism.</p><p><b>METHODS</b>A case control study of 106 patients with liver cirrhosis following HBV C infection was performed in comparison with 108 controls by PCR-RFLP.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Polymorphism of NOS2A promoter -969(G>C) is associated with portal hypertension of liver cirrhosis / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To determine whether polymorphism of NOS2A promoter -969G>C is associated with the portal hypertension of liver cirrhosis.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

The association of HLA-DRB1 allele polymorphism with the genetic susceptibility to liver cirrhosis due to hepatitis B virus / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of human leucocyte antigen (HLA)-DRB1 allele with the genetic susceptibility to cirrhosis due to hepatitis B virus(HBV).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>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.</p>