NM_000669.4(ADH1C):c.815G>A (p.Arg272Gln) AND Alcohol dependence

Clinical significance:protective (Last evaluated: Jun 1, 2008)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000019810.2

Allele description [Variation Report for NM_000669.4(ADH1C):c.815G>A (p.Arg272Gln)]

NM_000669.4(ADH1C):c.815G>A (p.Arg272Gln)

Gene:
ADH1C:alcohol dehydrogenase 1C (class I), gamma polypeptide [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
4q23
Genomic location:
Preferred name:
NM_000669.4(ADH1C):c.815G>A (p.Arg272Gln)
Other names:
ADH1C, ARG272GLN (rs1693482)
HGVS:
  • NC_000004.12:g.99342808C>T
  • NG_011718.1:g.14953G>A
  • NM_000669.4:c.815G>A
  • NP_000660.1:p.Arg272Gln
  • NC_000004.11:g.100263965C>T
  • NM_000669.3:c.815G>A
  • NR_133005.1:n.1154+31G>A
  • P00326:p.Arg272Gln
Protein change:
R272Q; ARG272GLN
Links:
UniProtKB: P00326#VAR_000428; OMIM: 103730.0001; dbSNP: rs1693482
NCBI 1000 Genomes Browser:
rs1693482
Molecular consequence:
  • NR_133005.1:n.1154+31G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000669.4:c.815G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Alcohol dependence
Synonyms:
ALCOHOL DEPENDENCE, PROTECTION AGAINST
Identifiers:
MedGen: C0001973; OMIM: 103780

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000040108OMIMno assertion criteria providedprotective
(Jun 1, 2008)
germlineliterature only

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

The gamma 1 and gamma 2 subunits of human liver alcohol dehydrogenase. cDNA structures, two amino acid replacements, and compatibility with changes in the enzymatic properties.

Höög JO, Hedén LO, Larsson K, Jörnvall H, von Bahr-Lindström H.

Eur J Biochem. 1986 Sep 1;159(2):215-8.

PubMed [citation]
PMID:
3758060

The genetics of alcohol metabolism: role of alcohol dehydrogenase and aldehyde dehydrogenase variants.

Edenberg HJ.

Alcohol Res Health. 2007;30(1):5-13. Review.

PubMed [citation]
PMID:
17718394
PMCID:
PMC3860432
See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000040108.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (4)

Description

The ARG271GLN variant has been designated as R272Q based on numbering which includes the translation initiation codon (Edenberg, 2007).

Hoog et al. (1986) found 2 amino acid differences between the gamma-1 and gamma-2 alleles: an arg272-to-gln (rs1693482) substitution in exon 6 and an ile350-to-val (I350V; 103730.0002) substitution in exon 8 of the ADH1C gene. They determined that the R272Q substitution was responsible for the differences in enzymatic properties, whereas the I350V substitution had no special importance. The location of R272Q appeared important for total charge and catalytic properties, as well as NADH coenzyme interaction.

The gamma-1 allele, now known as ADH1C*1, was originally defined as a gamma subunit that has arg272 and ile350 (Hoog et al., 1986). In almost all cases, these 2 SNPs are in linkage disequilibrium with one another. The gamma-2 allele, now known as ADH1C*2, has gln272 and val350. Homozygosity for the ADH1C*1 allele has a 70% higher turnover rate than homozygosity for ADH1C*2 allele (Edenberg, 2007).

Chai et al. (2005) examined ADH1B, ADH1C, and ALDH2 polymorphisms in 72 alcoholic and 38 nonalcoholic healthy Korean men; 48 patients had type I alcoholism, and 24 had type II alcoholism. The frequency of ADH1B*1 (103720.0001) and ADH1C*2 alleles was significantly higher in men with type II alcoholism than in men with type I alcoholism and in healthy men. The frequency of the ALDH2*1 (100650.0001) allele was significantly higher in men with alcohol dependence (103780) than in healthy men. Chai et al. (2005) suggested that the genetic characteristics of alcohol metabolism in type I alcoholism fall between nonalcoholism and type II alcoholism.

Among 9,080 Caucasian Danish men and women using the Michigan Alcohol Screening Test, Tolstrup et al. (2008) found that men heterozygous or homozygous for the slower metabolizing ADH1C*2 allele had a 40 to 70% higher risk for heavy or excessive alcohol intake compared to those homozygous for the fast metabolizing ADH1C*1 allele. Similar results were found for women, but effect sizes were smaller and reached significance only for heavy drinking.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 30, 2019

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