Polymorphism Of Aldehyde Dehydrogenase 2 (ALDH2) Gene And Correlation Between Drinking And Kidney Stones

[Objective] To evaluate the impact of acetaldehyde dehydrogenase-2(ALDH2)polymorphism and alcohol drinking on kidney stones risk.[Methods] A total of 2080 kidney stones patients and 4317 healthy controls from 12 hospitals in Guangxi of china were enrolled in this study.We matched and analyzed data from 1010 cases and 1010 controls based on their sex,age,and resident area.DNA was extracted for peripheral blood and ALDH2(rs671)genotypes were examined by SNPscan TM high-throughput SNP classification technology.We also included 89 kidney stones patients and 89 age-matched controls from Fangchenggang Area Health and Examination Survey(FAMHES)cohort.The Illumina Omni 1 platform was used for a genome-wide assay of samples in FAMHES.The chi-square test was used to compare the differences between two groups and the multi-variable binary logistic regression was used to calculate the odds ratio(OR)and 95% confidence interval(95% CI).[Results] The frequency of ALDH2 variant genotypes(GA/AA)in kidney stones patients and controls were 456(53.1%)and 402(46.9%)respectively.Alcohol consumption was found in 528(54.0%)kidney stones patients and 449(46.0%)controls.The Body mass index(BMI)and systolic pressure was significantly higher in kidney stones patients(P=0.00).ALDH2 variant genotypes(GA/AA)showed an increased risk of developing kidney stones(OR=1.37,95%CI=1.10-1.57)compared with ALDH2 wild genotype(GG).Alcohol consumption increased risk for kidney stone as indicated by an OR of1.34(95%CI=1.12-1.60)in alcoholic drinkers.In addition,we observed significant interaction between ALDH2 and alcohol consumption in kidney stones risk(OR=1.31,95%CI=1.00-1.72).Furthermore,when compared with non-alcoholic drinkers carried ALDH2 wild genotypes(GG),alcoholic drinkers carried ALDH2 variant genotypes(GA/AA)showed an elevated risk of developing kidney stones(OR=1.71,95%CI=1.30-2.25).[Conclusions] ALDH2 polymorphism(rs671)and alcohol consumption are associated with kidney stones risk.ALDH2 variant genotypes(GA/AA)carriers have a significant increased risk of developing kidney stones,especially among alcoholic drinkers.Our study reveals a significant role of gene-environmental interaction in kidney stones risk.[Objective] To study the relation between acetaldehyde dehydrogenase-2(ALDH2)genotypes and alcohol consumption and the susceptibility of kidney stones in calcium oxalate calculus models of mice,and to explore the risk factors of kidney stones.[Methods] 18 ALDH2 gene knockout(ALDH2-/-)and 18 ALDH2 wild type(ALDH2 + / +)eight weeks old of male ICR mice were randomly divided into three groups: normal control group,ethylene glycol(EG)group,drinking group,six mice in each group.The normal control group were treated whit purified water and ordinary feed,the EG group were treated with 0.75%EG and ordinary feed,the drinking group were treated with 4 g/kg ethanol(every day)for 6 wk.End of the test,blood,urine and renal tissue were collected and kept respectively,The content of Ca2 +,creatinine,uric acid,Beta-N-acetyl amino glycosidase enzymes(NAG)in the urine were measured,and the serum creatinine,uric acid and Ca2 + were measured.One renal tissue was imbedded in paraffin,and histological section(5?m),HE stain,the formation of oxlate renal stone was observed by polarization microsopy,the other side kidney was usedto detect the 4-HNE,MDA content.One-way ANOVA analysis and LSD(L)test was used to compare the differences between groups.[Results] The body weight of drinking group is lower than normal control group and EG group.In ALDH2(-/-)mice,urine creatinine of drinking group was obviously higher than the normal control group and ethylene glycol group.The level of 4-HNE is same to the MDA,1.Both ALDH(+/+)and ALDH(-/-)mice,drinking group is higher than normal control group.2.In ALDH(-/-)mice,drinking group is higher than EG group.3.In drinking group,ALDH(-/-)mice is higher than ALDH(+/+)mice.Not only in the ALDH(-/-)mice but also in the ALDH(+/+)mice,Urinary NAG activity also increased in drinking group compared whit other groups.Comparing kidney crystallization score between all groups have shown:1.In both ALDH(+/+)and ALDH(-/-)mice,drinking group and EG group is higher than normal control group.2.In ALDH(-/-)mice,drinking group is higher than EG group.3.In drinking group,ALDH(-/-)mice is higher than ALDH(+/+)mice.[Conclusions] Our study reveals a significantly combined effect(geneenvironment interaction)between alcohol consumption and ALDH2 polymorphism for the risk of kidney stone.Comapared to the wild type mice,ALDH2(-/-)mice exposing to alcohol have a higher level of 4-HNE and the MDA suggesting the enhanced production of ROS,a higher level of urinary NAG suggesting the potential kidney damage,and a higher renal pathology crystallization score suggesting the potential formation of kidney stone.