Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Liver alcohol dehydrogenase oxidizes ethanol to acetaldehyde, which is further oxidized to acetate by aldehyde dehydrogenase-2 (ALDH2*1). Individuals who carry a low-activity ALDH2 (ALDH2*2) display high blood acetaldehyde levels after ethanol consumption, which leads to dysphoric effects, such as facial flushing, nausea, dizziness, and headache ("Asian alcohol phenotype"), which result in an aversion to alcohol and protection against alcohol abuse and alcoholism. Mimicking this phenotype may reduce alcohol consumption in alcoholics. RNA interference (RNAi) is a cell process in which a short interfering RNA (siRNA) of 21-25 bp guides the degradation of a complementary target mRNA. Thus, siRNAs may be useful in mimicking the Asian phenotype by inhibiting ALDH2 gene expression. We determined the inhibitory effect of three chemically synthesized siRNAs targeted against rat ALDH2 mRNA in human embryonic kidney cells (HEK-293 cell lines) transfected with a plasmid carrying the rat ALDH2 cDNA. Two of the three siRNAs were active, yielding a 65-75% reduction of ALDH2 activity. Based on the most promising siRNA sequence, three short hairpin RNA (shRNA) genes driven by the human U6 RNA promoter were designed and cloned in a plasmid. After transfection of HEK-293 cells, one of the genes was shown to be active, yielding a 50% reduction of ALDH2 activity. This effect is consistent with a 50% reduction in ALDH2 mRNA, whereas neither beta-actin mRNA nor the interferon-inducible transmembrane protein-1 mRNA levels were affected. This study describes chemically synthesized siRNAs and an endogenously synthesized shRNA, which reduce ALDH2 activity and constitute tools that should be of value for further alcohol research.
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PMID:RNA interference against aldehyde dehydrogenase-2: development of tools for alcohol research. 1925 Nov 11

Three single nucleotide polymorphisms (SNPs) in alcohol-metabolizing genes - ADH1B (Arg47His), ADH1C (Ile350Val) and ALDH2 (Glu504Lys) have been extensively associated with flush reaction and alcoholism. Therefore, we investigated the association of these three SNPs with alcohol-induced reactions (AIRs), alcoholism risk, personality and anthropometric traits among Malaysian university students. AIRs, Self-Rating of the Effects of Alcohol (SRE) and Ten-Item Personality were surveyed, anthropometric measurements and DNA samples were taken. Among 264 valid drinkers (111 males, 153 females; 229 ethnic Chinese, 35 ethnic Indians), the minor allele frequencies for ADH1B, ADH1C, ALDH2 among Chinese/Indians were .45/.07, .33/.40, .32/.41, respectively; distribution of ADH1B alleles significantly different between ethnicities. Current/former experiences of flushing, hives, heart palpitations after alcohol consumption; and sleepiness, headache reactions, early and overall SRE were significantly different between ethnicities and genders, respectively. Overall SRE score was associated with ADH1C and ALDH2 alleles. 'Openness to Experiences' was associated with ALDH2 genotypes and alleles; Glu/Glu or Glu carriers showed significantly higher means. ADH1B Arg/Arg and Arg carriers showed significantly higher total body and subcutaneous fats but association was abolished after controlling for ethnicity. In conclusion, gender and ethnicity, but not alcohol-metabolizing gene variants, play a role in influencing the manifestation of AIRs.
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PMID:Genetic polymorphisms of alcohol-metabolizing enzymes and their association with alcoholism risk, personality and anthropometric traits among Malaysian university students. 2861 Apr 54