Relationship Between HMGB1 Gene Polymorphism And Alcoholic Liver Disease

Objective: Alcoholic liver disease is a disease with mutual influence of heredity,environment and lifestyle,and the etiology and mechanism are still unclear.Currently,there are many studies on high mobility group protein box 1 gene polymorphism and viral hepatitis and non-alcoholic liver disease.Therefore,this paper aims to prove whether1177G/C in HMGB1 is associated with alcoholic liver disease(ALD)in Inner Mongolia through experiments,and to explore whether HMGB1 gene polymorphism is a high risk factor for ALD.This study can be used as a preliminary experiment.Next,the subject will classify the subjects according to the clinical symptoms of TRADITIONAL Chinese medicine,and obtain the GG/GC/CC classification and proportion of the samples through the experiment,which is combined with the TRADITIONAL Chinese medicine classification of ALD patients,providing theoretical basis for further discussion on the prevention and treatment of ALD from the perspective of genes.Methods: From January 2019 to July 2020,a total of 516 cases of physical examiners,inpatients and inpatients of The Second People’s Hospital of Ordos who met relevant standards in the Physical Examination Center of the First Affiliated Mongolian Traditional Chinese Medicine Hospital of Inner Mongolia Medical University and the Second People’s Hospital of Ordos were selected as the research objects.There were 129 patients in the control group,including 114 males and 15 females,aged 27-72(47.43±11.03)years,BMI(25.28±2.97)kg/m2;In the alcoholic group,143 patients,134 males and 9 females,aged25-67(46.20±11.87)years,BMI(26.20±3.07)kg/m2;There were 126 patients with alcoholic liver disease,117 males and 9 females,aged 25-73(49.42±12.08)years,BMI(28.20±3.67)kg/m2;Non-alcoholic liver disease group consisted of 118 patients,107 males and 11 females,aged 25-72(47.39±11.92)years old,BMI(26.27±3.68)kg/m2.Meanwhile,the polymorphism of HMGB1 1177G/C in each group was detected by POLYMERase chain reaction.Hardy-weinberg equilibrium was used to test whether SNP conformed to H-W equilibrium.Logistic regression analysis was used for correlation analysis.Results:1.A total of 516 subjects were included in this study,including 129 in the normal group with an average age of 47.43 years,143 in the alcoholic group with an average age of 46.20 years,126 in the alcoholic liver group with an average age of 49.42 years,and 118 in the non-alcoholic liver group with an average age of 47.39 years.There was no significant difference in age and sex among the four groups(P > 0.05).BMI was the lowest in the normal group,and the highest in the alcoholic liver disease group,with statistical significance(P < 0.05).2.Haploview software was used to carry out Hardy-Weinberg equilibrium test for SNP loci.The distribution of GG,GC and CC genotypes(2=0.603,P =0.437)in the control group was consistent with Hardy-Weinberg equilibrium law,achieving genetic equilibrium and representing the population.The genotype frequency distribution of HMGB1 gene loci was significantly different among the four groups(P < 0.001).The results showed that GG(48.3%)genotype frequency of non-alcoholic liver disease group was lower than the other three groups,while CC(22.0%)genotype frequency was higher than the other three groups.In alcoholic liver disease group,CC(11.1%)genotype frequency was higher than alcoholic group(3.5%),while GC(26.2%)genotype frequency was lower than alcoholic group(32.2%).The allele frequency distribution of HMGB1 gene locus in each group was statistically significant(P < 0.001).The frequency of G(63.1%)allele was lower than that of the other three groups,while C(36.9%)allele was higher than that of the other three groups.The G allele frequency of alcoholic liver disease group(75.8%)was lower than that of alcoholic group(80.4%),while the C allele frequency of alcoholic liver disease group(24.2%)was higher than that of alcoholic group(19.6%).There was no significant difference in allele frequency between normal group and alcoholic group(P > 0.05).3.Model 1 was set as the coarse model,and Model 2 was adjusted for age,sex and BMI.The results of the comparison between the alcoholic liver disease group and the normal group showed that GG+GC genotype was a protective factor for ALD compared with CC genotype in the dominant model after adjusting for age,sex,and BMI(OR=0.25,95%CI: 0.08-0.90,P =0.019).There was no correlation between genotype and ALD in recessive model and shared model.The results of the comparison between the non-alcoholic liver disease group and the normal group showed that GG+GC genotype was a protective factor for the development of non-alcoholic liver disease compared with CC genotype in the dominant model after adjusting for age,sex and BMI(OR=0.14,95%CI:0.05-0.39,P < 0.001).In recessive model,GG genotype was a protective factor of non-alcoholic liver disease compared with GC+CC genotype(OR=0.41,95%CI: 0.24-0.68,P =0.001).In the shared model,genotype from CC to GC to GG was associated with a reduced risk of nonalcoholic liver disease(OR=0.43,95%CI: 0.29-0.64,P < 0.001).In the dominant model,GG+GC genotype was a protective factor for ALD compared with CC genotype after adjusting for age,sex and BMI(OR=0.29,95%CI: 0.10-0.83,P =0.021).There was no correlation between genotype and ALD in recessive model and shared model.In the dominant model,GG+GC genotype was a protective factor for ALD compared with CC genotype after adjusting for age,sex and BMI(OR=0.31,95%CI: 0.13-0.71,P =0.006).There was no correlation between genotype and ALD occurrence in recessive and shared models.Conclusion:1.HMGB1 gene polymorphism is correlated with alcoholic liver disease in Inner Mongolia.2.Allele G may be a protective factor for alcoholic liver disease and non-alcoholic liver disease.3.People with the CC genotype have a higher risk of developing non-alcoholic liver disease.4.Allele C may be a risk factor for alcoholic liver disease.