Studies On The Relationship Between The Polymorphisms Of MTHFR, IL-10, ALDH2 And The Outcome Of HBV Infection

How the disease evolves after HBV infection is effected by a variety of factors such as host and virus. Host gene polymorphism is likely to influence disease progression after HBV infection. Gene polymorphism has a strong regional and national identity, and the results of studys connerning on the the relationship between polymorphisms and liver disease varied in different regions and ethnics. Thereby, analyzing the influence of MTHFR, IL-10, ALDH2 gene polymorphisms and disease progression after HBV infection in Chinese Han population in Tianjin may contribute to in-depth study on the etiology of liver disease occurrence in this region.AIM:To investigate the relationship between MTHFR, IL-10, ALDH2 polymorphisms and the outcome of HBV infection.METHODS:Collect 955 samples as follows:205 healthy control subjects,161 self-limited patients infected with HBV,221 patients with chronic hepatitis B,172 patients with HBV-induced liver cirrhosis and 236 cases with HBV-related HCC. Genome DNA was extracted from clot, TaqMan SNP genotyping and sequencing assays were employed to determine the distribution of genotypes and alleles at five sites in three genes as MTHFR 677 C/T, IL-10-1082 A/G,-819 T/C and ALDH2 rs4646778 C/A, rs671 A/G. Row×Column or revisedχ2 examination were used to analyse genotype and allele at the positions above. IL-10-1082/-819 and ALDH2 rs4646778/rs671 haplotype were also analysisied in all the groups.RESULTS:1. MTHFR:Of the 805 subjects, genotype CT, TT and CC accounted for 47.09%,30.43% and 22.48%, respectively. The frequency of C allele was 46.02% and T was 53.98% of the total subjects, which are significantly different from other areas and races. Analysis on the distribution of genotypes in different sexes showed that males with TT genotype had a reduced risk with liver diseases. Particularly, the odds ratio (OR) of TT and CT was lowest in the liver cirrhosis group versus self-limited group. In contrast, females with TT and CT genotypes had an increased risk in the self-limited, chronic hepatitis and liver cirrhosis groups. Particularly, the liver cirrhosis group had the highest OR value versus self-limited group. However, females with TT and CT had a reduced risk in HCC group versus self-limited group. There was no significant difference about the genotype and allele distribution in different clinical feature groups such as Child-Pugh liver faction classification, AFP level in liver cirrhosis and HCC patients, HBsAg expression and DNA copies in all patients with liver disease.2. IL-10:Of the 700 subjects, genotype AA, AG and GG of IL-10-1082 accounted for 82.29%,16.00% and 1.71%, respectively, the frequency of A allele was 90.29% and T was 9.71%of the total subjects, while genotype TT, TC and CC of IL-10-819 accounted for 41.43%,48.14%, and 10.43%, respectively, the frequency of T allele was 65.64% and C was 34.36% of the total subjects. There was no significant difference of genotype or allele distribution among different groups at the two positions(P>0.05). Taking self-limited group as control,-1082 AG genotype and G allele decreased the risks of chronic hepatitis B and cirrhosis occurrence,-819 TC genotype decreased the risk of HCC, CC genotype and C allele decreased the risks of all the three liver disease groups. Analyzing distribution of haplotype-1082/-819 in each group showed that AC haplotype decreased the risks of cirrhosis and HCC using healthy or self-limited group as control, and the reduction degree was greater when regarding self-limited group as control, GC haplotype decreased the risks of chronic hepatitis B and cirrhosis occurrence using self-limited group as control. Comparing IL-10 genotype and allele frequencies in different groups with different clinical features revealed that frequency of-819 C was significantly higher in patients with DNA<103 copies/mL than those with DNA≥103 copies/mL(P=0.025). In addition, There was no significant difference about the genotype and allele distribution in other clinical feature groups(P>0.05).3. ALDH2: Of the 180 subjects, genotype CC, CA and AA of ALDH2 rs4646778 accounted for 51.11%,37.78% and 11.11%, respectively, the frequency of C allele was 70.00% and A was 30.00% of the total subjects, while genotype GG, GA and AA of ALDH2 rs671 accounted for 72.22%,24.45%, and 3.33%, respectively, the frequency of G allele was 84.44% and A was 15.56% of the total subjects. There was no significant difference of genotype or allele distribution among different groups at the two positions(P>0.05). Take healthy group as control, rs4646778 CA genotype decreased the risks of all the three liver disease groups, C allele decreased the risks of HCC group. Analyzing distribution of haplotype rs4646778/rs671 in each group showed that AG and CA haplotype decreased the risks of all the three liver disease groups. There was no significant difference about the genotype and allele distribution in different clinical feature groups(P>0.05).CONCLUSION:1. MTHFR:The TT genotype shows a relatively high frequency in Tianjin, which is significantly different from other country or area. At the same time, MTHFR 677 polymorphism may play a role in influencing disease progression in patients with HBV infection, and the effect is different on different genders.2. IL-10: IL-10-1082 AG genotype and G allele,-819 TC, CC genotype and C allele,-1082/-819 AC, GC haplotype may play a protective role on disease progression after HBV infection.-819 C allele may attribute to virus elimination for HBV infected patients.3. ALDH2:rs4646778 CA genotype, C allele, and rs4646778/rs671 AG and CA haplotype may play a protective role on disease progression after HBV infection.