ALDH2 and Stroke: A Systematic Review of the Evidence

Xu, Haixia; Zhang, Yingmei; Ren, Jun

doi:10.1007/978-981-13-6260-6_11

Cited by 19 publications

(16 citation statements)

References 92 publications

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“…In the male Japanese population, the ALDH2 rs671 GG genotype is associated with cerebral lacunar infarcts 17 . In contrast, presence of the ALDH2 rs671 A allele could be a risk factor for cerebral infarction in Han-Chinese population 15 . A reduction in ALDH2 activity may interfere with endothelium angiogenesis and is associated with cerebral amyloid angiopathy 18 .…”

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confidence: 83%

“…Previous studies suggested an association between genetic variants in the alcohol metabolism pathway and vascular diseases 14 . Individuals with the ALDH2 rs671 A allele have higher prevalence of hypertension, cardiovascular risk factors, and cerebral infarction 15 . Polymorphisms in ALDH2 rs671 are associated with coronary artery disease (CAD) in Chinese patients with hypertension 16 .…”

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confidence: 99%

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Association of alcohol dehydrogenase and aldehyde dehydrogenase Polymorphism with Spontaneous Deep Intracerebral Haemorrhage in the Taiwan population

Huang

Chang

Lee

et al. 2020

Sci Rep

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Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) encode essential alcoholmetabolizing enzymes. While alcohol use is associated with spontaneously deep intracerebral haemorrhage (SDicH), particularly in males, the activities and genetic variants of ADH and ALDH may affect SDICH development. This case-control study was conducted to identify the interaction of alcohol use and SDICH with five single-nucleotide polymorphisms (SNPs): ADH1B rs1229984, ADH1C rs2241894, ALDH2 rs671, ALDH2 rs886205, and ALDH2 rs4648328. We enrolled 208 patients with SDICH and 244 healthy controls in a Taiwanese population. ALDH2 rs671 was significantly associated with SDicH in the dominant (P < 0.001) and additive models (P = 0.007). ALDH2 rs4648328 was borderline significantly associated with SDICH in the recessive (P = 0.024) or additive models (P = 0.030). In alcohol-using patients, the ALDH2 rs671 GG genotype was associated with SDICH risk compared to the GA+AA genotype (P = 0.010). ADH1B rs1229984, ADH1C rs2241894, and ALDH2 rs886205 did not demonstrate association with SDicH. thus, the ALDH2 rs671 GG genotype is a risk factor for SDICH. Because the genetic distributions of ALDH2 rs671 exhibited strong ethnic heterogeneity, further studies in different populations are needed to validate these findings. Primary intracerebral haemorrhage (ICH), accounting for 22-35% of all cases of stroke in Asian populations 1 , is the most devastating stroke subtype with high rates of death and long-term disability in adults 2,3. Asian populations have higher incidences of primary ICH than Caucasians 2. Sixty to eighty percent of primary ICH cases occur at the non-lobar region, including the basal ganglia, thalamus, brain stem, and cerebellum, and are also known as spontaneously deep intracerebral haemorrhage (SDICH) 4. Numerous factors, such as hypertension and alcohol use, have been proposed to contribute to SDICH development 5,6. Alcohol use was associated with an increased ICH risk 7. Alcohol is primarily metabolized by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) 8. The metabolism of alcohol produces acetaldehyde, acetate, and reactive oxygen species (ROS). Excessively produced acetaldehyde and ROS, which are highly reactive and toxic by-products, are distributed throughout cell membranes and interact with certain proteins, affecting cell function and leading to organs damage. The accumulation of acetaldehyde causes oxidative damage, excessive autophagy, decreased myofilament calcium sensitivity, and impaired endoplasmic reticulum calcium-ATPase function 9. Acetate metabolism involved in lipid biosynthesis in the mitochondria of brain tissues 10. In animal models, toxic aldehydes enlarged the cerebral ischaemia-induced infarct area and increased oxidative stress 11,12. Deceased enzymatic activity of ALDH, a condition which impairs the degradation of acetaldehyde, could be

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confidence: 83%

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confidence: 99%

Association of alcohol dehydrogenase and aldehyde dehydrogenase Polymorphism with Spontaneous Deep Intracerebral Haemorrhage in the Taiwan population

Huang

Chang

Lee

et al. 2020

Sci Rep

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“…The significant aldehyde dehydrogenase 2 ( ALDH2 ) rs671 single‐nucleotide polymorphism (SNP; Glu504Lys) in exon 12, which causes a replacement of glutamate to lysine at position 504, results in the decreased catalytic ability of the enzyme encoded by this gene 3 . As a key enzyme in the ethanol metabolism pathway and an important anti‐oxidant stress molecule, Glu504Lys polymorphism of ALDH2 is significantly associated with the occurrence and development of cardio‐cerebrovascular diseases 3 , 4 , 5 .…”

Section: Introductionmentioning

confidence: 99%

Prospective study: Aldehyde dehydrogenase 2 gene is associated with cardio‐cerebrovascular complications in type 2 diabetes patients

Pan

Wang

et al. 2021

J of Diabetes Invest

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Aims/Introduction Most studies have shown that aldehyde dehydrogenase 2 (ALDH2) mutations were associated with cardio‐cerebrovascular complications of diabetes based on cross‐sectional investigations, but few studies based on cohorts were carried out. The aim of this study was to explore the correlation between the ALDH2 gene and the occurrence of and death from cardio‐cerebrovascular complications in type 2 diabetes patients through a prospective cohort study. Materials and Methods According to a community‐based and disease‐based prospective cohort study design, a baseline cohort of 10,339 persons with type 2 diabetes was established in 2016, and the occurrence of and death from cardio‐cerebrovascular complications were followed up until December 2018. A total of 2,500 diabetes patients without cardio‐cerebrovascular complications were randomly selected from the baseline cohort to detect the rs671 polymorphism of the ALDH2 gene. Cox regression analysis was carried out on the effect of different ALDH2 rs671 single‐nucleotide polymorphisms on the risk and survival time of cardio‐cerebrovascular complications among diabetes patients. Results There were 215 cardio‐cerebrovascular complications, including 10 deaths, that occurred in the 2,500 diabetes patients during the follow‐up period. Cox regression analysis showed that rs671 GA/AA genotype, sex (male), poor control of high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, blood pressure and glycated were risk factors, whereas drinking alcohol was a protective factor for cardio‐cerebrovascular complications (P < 0.05). After adjusting for age and sex, the risk of the rs671 GA/AA genotype was 1.314‐fold (95% confidence interval 1.000–1.727) that of the GG genotype. Conclusion The G‐A mutation of ALDH2 rs671 is a risk factor for the occurrence of and death from cardio‐cerebrovascular complications in type 2 diabetes patients. Further studies with larger cohorts and longer follow up will be necessary to reveal a consensus.

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“…In addition to its effect on alcohol consumption, rs671 polymorphism of ALDH2 is associated with hypertension, dyslipidemia, type 2 diabetes mellitus, and cardiovascular diseases (14,15). Recent studies have suggested that ALDH2 is associated with SUA levels and gout susceptibility (16,17).…”

Section: Introductionmentioning

confidence: 99%

Analysis of gender-specific associations between aldehyde dehydrogenase 2 (ALDH2) rs671 genetic polymorphisms and serum uric acid levels in Han Chinese

et al. 2021

Ann Transl Med

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Background: Serum uric acid (SUA) is influenced by lifestyle and genetics, and unbalanced SUA levels are linked to various common disorders. While the aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism appears to be associated with SUA levels, the evidence remains inconclusive. The aim of this study was to examine the distribution of the ALDH2 rs671 polymorphism among Han Chinese in Beijing and determine the association between this polymorphism and SUA.Methods: A total of 6,461 randomized healthy individuals were included in the study. Biochemical indicators were tested and ALDH2 rs671 polymorphism testing was conducted for subjects enrolled in the study. The distribution of the ALDH2 rs671 polymorphism and the relationship between genotype and the levels of serum lipids and uric acid (UA) were analyzed.Results: The ALDH2 rs671 genotype frequencies were 68.1% (G/G), 29.3% (G/A), and 2.6% (A/A).There was no significant difference in allele distribution between males and females. In males, different ALDH2 genotypes exhibited significant differences in several biochemical analytes, including body mass index (BMI), blood glucose (Glu), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), UA, glutamyl transpeptidase (GGT), and creatinine (Cr) (P<0.05). No such differences were found in females.

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ALDH2 and Stroke: A Systematic Review of the Evidence

Cited by 19 publications

References 92 publications

Association of alcohol dehydrogenase and aldehyde dehydrogenase Polymorphism with Spontaneous Deep Intracerebral Haemorrhage in the Taiwan population

Association of alcohol dehydrogenase and aldehyde dehydrogenase Polymorphism with Spontaneous Deep Intracerebral Haemorrhage in the Taiwan population

Prospective study: Aldehyde dehydrogenase 2 gene is associated with cardio‐cerebrovascular complications in type 2 diabetes patients

Analysis of gender-specific associations between aldehyde dehydrogenase 2 (ALDH2) rs671 genetic polymorphisms and serum uric acid levels in Han Chinese

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