Origin and dispersal of atypical aldehyde dehydrogenase ALDH2⁎487Lys

Luo, Huai‐Rong; Wu, Gui-Sheng; Pakstis, Andrew J.; Li, Tong; Oota, Hiroki; Kídd, Kenneth K.; Zhang, Yaping

doi:10.1016/j.gene.2008.12.021

Cited by 74 publications

(81 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These alleles were almost entirely confined to East Asian populations and originated in southern East Asia. Similarly, the frequency of the ALDH2*504Lys allele was the highest in Southeast China, and occurred in most areas of Asia with frequencies that gradually declined radially from Southeastern China [21,22]. The distribution of allele A in the SCN5A polymorphism was similar to that of these alleles.…”

Section: Discussionmentioning

confidence: 69%

The global distribution of the p.R1193Q polymorphism in the SCN5A gene

et al. 2016

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 69%

The global distribution of the p.R1193Q polymorphism in the SCN5A gene

et al. 2016

View full text Add to dashboard Cite

“…The Pai-Yuei people established an independent country in this area, which lasted for around 160 years until it was conquered by other tribes. The Yuei people then scattered to other areas of South and Southwest China, Vietnam, and Thailand where they integrated with other tribes, especially the Han tribe [27]. This scattering correlates with the distribution of the ALDH2*2 mutation amongst people of East Asian descent.…”

Section: Characterization Of Aldh2*2mentioning

confidence: 94%

“…Although the ALDH2*1 allele is most common in populations worldwide, the allele frequency of the ALDH2*2 variation as either homozygous or heterozygous is 35-45% in East Asians [8,26]. All individuals with ALDH2 enzymatic deficiency examined to date remarkably carry the same amino acid substitution, which can be traced back approximately 2000-3000 years to the Han Chinese [27]. Luo et al noted that the specific halpotype carrying the ALDH2*2 allele was highest in frequency in the Yunnan, South coastal, and East coastal areas of China and decreases in frequency further inland.…”

Section: Characterization Of Aldh2*2mentioning

confidence: 99%

Emerging Associations of the ALDH2*2 Polymorphism with Disease Susceptibility

Gueldner¹,

Sayes²,

Abel³

et al. 2016

J Drug Metab Toxicol

View full text Add to dashboard Cite

Ethanol is metabolized by Alcohol Dehydrogenase (ADH) to acetaldehyde and then irreversibly oxidized by Aldehyde Dehydrogenase (ALDH) to nontoxic acetate. In individuals expressing the ALDH2*2 variant enzyme, the rate of conversion from acetaldehyde to acetate is reduced and leads to flushing, nausea, and tachycardia due to increased blood levels of acetaldehyde. The ALDH2*2 variant has a lowered NAD + coenzyme binding affinity, which results in a lowered clearance capacity toward acetaldehyde. This polymorphism is caused by the substitution of glutamate for lysine at position 487 within the catalytic active site of ALDH2, resulting in effects on subunit and quaternary complex activity. ALDH2*2 alleles are dominant over ALDH2*1 and therefore are expected to contribute to the formation of inactive heterotetramers decreased enzymatic activity in both homozygous and heterozygous individuals. Consequently, a higher susceptibility to various diseases such as Alzheimer's, osteoporosis, and acute coronary syndrome has been associated with ALDH2*2 carriers. Additionally, the polymorphism seems to affect the efficacy of Glyceryl Trinitrate (GTN), a drug intended to treat coronary heart disease, in carriers of ALDH2*2 alleles. However, the polymorphism is believed to afford a protective effect against alcoholism as the side effects of acetaldehyde build-up are undesirable. Disulfiram, a drug historically used to treat alcohol dependency, induces the same undesirable physiological effects as the variant enzyme in non-carriers by inhibiting the normal functioning of ALDH2 enzyme.

show abstract

“…The acetate is further broken down into water and carbon dioxide and excreted by the body in urine and exhaled air. 7 Alcohol-related flushing occurs in some drinkers when acetaldehyde in the blood increases, usually as a result of slow conversion of acetaldehyde to acetate. Unger whose study of twins reported that in a Chinese sample experimentation with alcohol was more likely to be heritable compared to experimenting with tobacco, which was more likely to be familial.…”

Section: Alcohol and The Flushing Reactionmentioning

confidence: 99%

Social Meaning of Alcohol-Related Flushing Among University Students in China

Newman

Jinnai

Zhao

et al. 2011

Asia Pac J Public Health

View full text Add to dashboard Cite

This study explored drinking patterns, alcohol-related flushing, and ways students themselves and other people respond to flushing in drinking situations. Of 1080 Chinese undergraduate university students, 725 (67.1%) returned the completed surveys. 80% of the students were drinkers (93% of males and 69% of females); 68% of the drinkers were flushers.Most of the students (59.3%) said flushing had no special meaning, i.e. would ignore flushing; 54% of flushers said they could keep drinking "but less" when they flush; 27% of students said that a flushing person should stop drinking; however, if the flushing person is a girl, 89% of the students said the girl should drink less or stop. If the flushing person was a boy, 61% of students said he should drink less or stop. The data do suggest gender differences in the understanding of and social reaction to alcohol-related flushing, and these differences raise interesting questions as to how flushing acts as a potential protective factor against alcohol misuse.

show abstract

Origin and dispersal of atypical aldehyde dehydrogenase ALDH2⁎487Lys

Cited by 74 publications

References 42 publications

The global distribution of the p.R1193Q polymorphism in the SCN5A gene

The global distribution of the p.R1193Q polymorphism in the SCN5A gene

Emerging Associations of the ALDH2*2 Polymorphism with Disease Susceptibility

Social Meaning of Alcohol-Related Flushing Among University Students in China

Contact Info

Product

Resources

About