Association Of The Nco â…  Polymorphism At The Low-density Lipoprotein Receptor Gene With Hepatitis C And The Anlysis Of Interaction

Object:To study the relationship between Nco Ⅰp olymorphism located at the LDL-R geneexon18and hepatitis C, and to analyze the interaction between NcoⅠ a nd other factors.Providing clues for studying the mechanism of HCV infection, and scientific support forcomprehensive prevention and treatment.Methods:A total of86patients with Hepatitis C virus were recruited from the First AffiliatedHospital of University of South China, without anti-viral therapy, who were diagnosedbased on ‘Plan for prevention and treatment of viral hepatitis’(2000, Xi’an). As a control,88healthy individuals from the same hospital were included. Liver function and plasmalipid levels were detected for everyone. The Nco Ⅰ genotyping was determined byPCR-RFLP, the HCV-RNA load was tested by RT-PCR. And the relationship betweenNco Ⅰp olymorphism and Hepatitis C, the interaction between Nco Ⅰpolymorphism andother factors to Hepatitis C were analyzed by SPSS and Bootstrap.Results:1. No significant differences were seen between case and control in sex, age, residencetypes, vocations, education degree and the level of income, whereas regarding the bodymass index (BMI), we found that HCV-infected patients were significantly lower thanhealthy individuals (t=3.395, P=0.001). Patients with HCV infection had significantlylower TC, TG, HDL, LDL, ALB, A/G and higher TP, TBIL, DBIL, ALT, AST, IBIL, GLBthan did individuals without HCV infection. Regarding the life behavior of HCV-infectedpatients, tobacco (Z=-0.127, P=0.899) and activity (χ~2=4.155, P=0.125) were notassociated with the severity of CHC, but the different distribution of alcohol (χ~2=6.882,P=0.032) was observed among the light, the medium and the heavy.2. Among these174people in this study, the N~+allele frequency and N~-allelefrequency of NcoⅠ polymorphism at the LDL-R gene exon18locus were59.75%and 40.25%. In case, the Nco Ⅰg enotype distribution wasN~-N~-in15patients, N~+N~+in33andN~+N~-in38; In control, that was N~-N~-in18, N~+N~+in34and N~+N~-in36. The distributionwas in accordance with the Hardy-Weinberg equilibrium, but no significant differencewas observed between the two groups（χ~2=0.319, P=0.853）. The allele frequences of N~+and N~-in group of Hepatitis C (N~+60.5%, N~-39.5%) were similar to that in healthyindividuals (N~+59.1%, N~-40.9%).3. Among the86HCV-infected patients,58were positive for HCV RNA and28werenegative for HCV RNA. The allele (χ~2=0.144, P=0.705) and genotype (χ~2=0.448,P=0.799) distributions did not differ significantly between the two groups.4. As to HVC-infected patients, the mean HCV RNA load of patients with genotypeN~-N~-, N~+N~+and N~+N~-were1.12×10~6IU/ml,1.61×10~6IU/ml and1.13×10~6IU/ml, thedifference did not reach statistical significance (χ~2=0.456, P=0.796). The patients withHCV were divided into three groups by their condition: light (n=48), medium (n=24) andheavy (n=14).The allele frequences of these three groups were similar (χ~2=2.755,P=0.252), but the genotype distributions were different (χ~2=7.671，P=0.022).5. The HCV RNA load was not significantly associated with TC, HDL, TP, TBIL,DBIL, IBIL, the levels of activity and BMI, but significantly positive correlated withage(r_s=0.216, P=0.046), ALT(r_s=0.390, P=0.000),AST(r_s=0.319, P=0.000),GLB(r_s=0.269,P=0.012), alcohal(r_s=0.241, P=0.025), and negative correlated with TG (r_s=-0.222,P=0.040), LDL(r_s=-0.253, P=0.019), ApoB(r_s=-0.278, P=0.010), ALB(r_s=-0.351,P=0.001) and A/G(r_s=-0.348, P=0.001).6. The Ordinal Mutinomial Logistic Regression and Classification tree model showedthat age, genotype of Nco Ⅰp olymorphism at the LDL-R gene exon18locus, vocationand alcohol were significantly associatied with the state of Hepatitis C. As the age(B=0.108, P=0.001), the alcohol consumption (B=0.061, P=0.021) increased, the illnessgot worse, especially in patients older than35(χ~2=21.048, P=0.000) and alcohol intakeof more than2.37g/d(χ~2=9.789, P=0.009). Genotype N~-N~-(OR=5.812, P=0.021) was arisk factor for CHC exacerbations, but working with knowledge and technic (OR=0.125,P=0.008) was a protective factor.7. The interaction of Nco Ⅰg enotype andalcohol consumption, Nco Ⅰgenotype and thelevels of activity were not seen. Conclusions:1. The polymorphism of Nco Ⅰl ocus at the LDL-R gene exon18has been identified,the N~+allele frequency is59.75%and N~-allele frequency is40.25%.2. The NcoⅠ p olymorphism at the LDL-R gene exon18is not associated with thesusceptibility of HCV infection and HCV RNA load. But the association between theNcoⅠ polymorphism and the state of Hepatitis C has been confirmed in this study. Wefound that the patients who carry N~-N~-genyotype (OR=5.812) are more likely to sufferfrom heavy Hepatitis C than those carry N~+N~-genotype.3. The HCV RNA load does positive correlate with age, ALT, AST, GLB, alcoholconmuption, but negative with TG, LDL, ApoB, ALB and A/G.4. The patients’ condition could be associated with age, vocation, Nco Ⅰgenotype andalcohol consumption, indicating the individuals who are older than35, carried N~-N~-genotype, working with no knowledge and technic, alcohol consumption higher than2.37g/d are more dangerous than others to suffer from heavy Hepatitis C.