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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.

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.

Objective: To study the pathological changes of splenic artery wall in portal hypertensive patients., Methods: The pathological changes and iNOS activity of splenic artery wall were studied in 21 patients with liver cirrhosis and 15 normal subjects, using light and electron microscope and immunohistochemistry., Results: Compared with normal individuals, the splenic artery of cirrhotic patients showed that the intima was thickened, split and broken, and the smooth muscle layer of middle membrane was thicker and migrated to underintima space. In cirrhotic patients, regression, atrophy or hypertrophy and hyperplasia were seen in smooth muscle cells whose contractile phenotype changed to synthetic phenotype as well. iNOS activated obviously. Extracellular matrix increased in the wall, resulting in collagenic and fibrous changes., Conclusions: Hemodynamic alteration due to liver cirrhosis induced pathological changes of splenic artery, including the damage to contractile structure and increase of iNOS activity. It is one of the reasons of decrease of artery reaction to contractile vasoactive materials.