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.
探讨ADH4外显子 rs1126671和ADH7 外显子rs971074多态性与危险饮酒行为及酒精性肝病的关联。采用回顾性病例对照研究方法,分析2021年11月至2022年6月河池市人民医院消化内科确诊的酒精性肝病患者,其中52例阳性危险饮酒行为酒精性肝病病例组,同性别同年龄段的103例阳性危险饮酒行为非酒精性肝病和105例无危险饮酒行为的健康体检者分别作为对照组。采用免疫比浊法检测血清总蛋白和白蛋白,差值法计算球蛋白;采用亚硝酸盐氧化法检测总胆红素和直接胆红素,差值法计算间接胆红素;采用底物法检测碱性磷酸酶、天门冬氨酸氨基转移酶、丙氨酸氨基转移酶和γ-谷氨酰基转移酶。结果显示,52例酒精性肝病患者全部为男性,采用三组间非参数独立样本Kruskal-Wallis检验分析酒精性肝病组、阳性饮酒行为组、健康对照组12项肝功能基线显示三组间M(Q1,Q3)分别为:血清总蛋白(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);白蛋白(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);直接胆红素(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);碱性磷酸酶(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);白蛋白比球蛋白比值1.34(0.91,1.88)、1.82(1.65,2.00)、1.89(1.68,2.07)(H=11.047,P=0.004);直胆胆红素比间胆胆红素比值 0.91(0.69,1.91)、0.41(0.35,0.54)、0.42(0.34,0.54)(H=19.478,P<0.001);血清总胆红素(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);天门冬氨酸氨基转移酶(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);丙氨酸氨基转移酶(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-谷氨酰基转移酶(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)等10项主要肝功能指标差异有统计学意义;而在危险饮酒和健康组的两两比较中差异均无统计学意义。ADH4和ADH7两个位点遗传连锁平衡,三组样本中ADH4基因rs1126671位点以CC纯合基因型为主,无TT基因型,三组比较和任意两组比较中差异均无统计学意义。ADH7基因rs971074基因型在三组比较中差异具有统计学意义(χ2=9.370,P<0.05),CT基因型与CC基因型相比在危险饮酒行为组和酒精性肝病组、健康组和酒精性肝病组两两比较差异无统计学意义,在健康组和危险饮酒行为组差异有统计学意义(χ2=6.372,P=0.012)。RD组和HA组之间的遗传模式分析显示在超显性遗传模式差异有统计学意义(OR=2.92,95%CI:1.22~6.98;P=0.012),显性遗传模式中差异有统计学意义(OR=2.90,95%CI:1.26~6.64;P=0.008),共显性遗传模式中差异有统计学意义(OR=2.96,95%CI:1.24~7.08;P=0.032)和累加模式中差异有统计学意义(OR=2.46,95%CI:1.16~5.22;P=0.013)。综上,ADH7基因rs971074的CT基因型是阳性危险饮酒行为的风险因素,ADH家族仍有可能通过ADH7与危险饮酒行为的关联增加潜在酒精性肝病保护背景人群易感性。.