[Analysis of genetic association between exon polymorphisms of ADH4 and ADH7 and risky drinking behavior of alcoholic liver disease].

Abstract

To analyze the correlation of ADH4 exon rs1126671 and ADH7 exon rs971074 polymorphisms with risky drinking behaviors and alcoholic liver disease. The patients with alcoholic liver disease diagnosed in the Gastroenterology Department of the People's Hospital of Hechi from November 2021 to June 2022, including 52 cases of alcoholic liver disease with positive risky drinking behaviors, 103 cases of non-alcoholic liver disease with positive risky drinking behaviors of the same gender and age, and 105 healthy subjects with no risky drinking behaviors as control groups were retrospectively analyzed. The serum total protein and albumin are detected by immunoturbidimetry and globulin is calculated by the difference method; the serum total bilirubin and direct bilirubin are detected by the nitrite oxidation method and indirect bilirubin is calculated by the difference method; alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase and γ-glutamyl transferase are detected by the substrate method. The results revealed that all 52 patients with alcoholic liver disease were male. The non-parametric independent sample Kruskal-Wallis test was adopted to analyze the baseline of twelve liver functions among the alcoholic liver disease group, the risky drinking behavior group and the healthy control group, and it was found there was statistical significance in ten major liver function indicators in the difference comparison among the three groups like serum total protein (g/L) 65.0 (60.1, 71.4), 73.4 (70.3, 76.3), 72.4 (69.2, 76.2) (H=37.130, P<0.001); albumin (g/L) 36.1 (28.6, 42.9), 47.2 (45.0, 49.2), 47.5 (45.9, 49.5) (H=14.503, P=0.001); direct bilirubin (μmol/L) 10.1 (35.6, 34.0.1), 3.8 (3.1, 5.45), 4.2 (2.9, 6.0) (H=26.608, P<0.001); alkaline phosphatase (U/L) 106.0 (71.0, 164.0), 68.0 (57.5, 82.0), 70.0 (59.0, 87.0) (H=27.904, P<0.001); albumin to globulin 1.34 (0.91, 1.88), 1.82 (1.65, 2.00), 1.89 (1.68, 2.07) (H=11.047, P=0.004); direct bilirubin to indirect bilirubin 0.91 (0.69, 1.91), 0.41 (0.35, 0.54), 0.42 (0.34, 0.54) (H=19.478, P<0.001); serum total bilirubin (μmol/L) 23.9 (13.7, 51.0), 13.8 (10.2, 17.9), 13.0 (10.1, 17.4) (H=18.375, P<0.001); aspartate aminotransferase (U/L) 74.0 (39.0, 122.0), 22.0 (19.0, 28.0), 23.0 (19.0, 30.0) (H=76.365, P<0.001); alanine aminotransferase (U/L) 37.0 (25.0, 55.0), 23.0 (17.0, 30.0), 24.0 (17.0, 33.8) (H=57.041, P<0.001); γ-glutamyl transferase (U/L) 135.0 (45.0, 364.0), 33.0 (23.5, 49.5), 32.0 (19.0, 49.0) (H=82.558, P<0.001); however, there were no statistical significance in the pairwise comparisons between risky drinking and healthy groups. The two loci of ADH4 and ADH7 were in genetic linkage equilibrium. In the three groups of samples, the ADH4 gene rs1126671 locus was comprised primarily of the CC homozygous genotype, and there was no TT genotype. The ADH7 gene rs971074 genotype had statistical difference in the comparison of the three groups (χ²=9.370, P<0.05). Compared with the CC genotype, the CT genotype had no statistical difference in the pairwise comparison between the risky drinking behavior group and alcoholic liver disease group, and the healthy group and alcoholic liver disease group. There was a statistical difference in that between the healthy group and the risky drinking behavior group (χ²=6.372, P=0.012). The analysis display of mode of inheritance between RD group and HA group was statistically significant in the difference of the superdominance inheritance mode (OR=2.92, 95%CI:1.22-6.98; P=0.012), the dominant inheritance mode (OR=2.90, 95%CI:1.26-6.64; P=0.008), the co-dominant inheritance mode (OR=2.96, 95%CI:1.24-7.08; P=0.032) and the additive mode (OR=2.46, 95%CI:1.16-5.22; P=0.013). In general, the CT genotype of ADH7 gene rs971074 is a risk factor for positive risky drinking behavior, and the ADH family may still increase the susceptibility of people with a potential alcoholic liver disease protection background through the correlation between ADH7 and risky drinking behavior.