NM_000212.2(ITGB3):c.176T>C (p.Leu59Pro) AND Myocardial infarction

Clinical significance:risk factor (Last evaluated: Jan 1, 2007)

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:
RCV000014522.6

Allele description [Variation Report for NM_000212.2(ITGB3):c.176T>C (p.Leu59Pro)]

NM_000212.2(ITGB3):c.176T>C (p.Leu59Pro)

Gene:
ITGB3:integrin subunit beta 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q21.32
Genomic location:
Preferred name:
NM_000212.2(ITGB3):c.176T>C (p.Leu59Pro)
HGVS:
  • NC_000017.11:g.47283364T>C
  • NG_008332.2:g.34523T>C
  • NM_000212.2:c.176T>C
  • NP_000203.2:p.Leu59Pro
  • LRG_481t1:c.176T>C
  • LRG_481:g.34523T>C
  • LRG_481p1:p.Leu59Pro
  • NC_000017.10:g.45360730T>C
  • NG_008332.1:g.34523T>C
  • P05106:p.Leu59Pro
Protein change:
L33P; LEU33PRO
Links:
UniProtKB: P05106#VAR_003993; OMIM: 173470.0006; dbSNP: rs5918
NCBI 1000 Genomes Browser:
rs5918
Molecular consequence:
  • NM_000212.2:c.176T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Myocardial infarction
Synonyms:
Myocardial infarction, susceptibility to; Heart attack; MI
Identifiers:
MedGen: C0027051; Human Phenotype Ontology: HP:0001658

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000034773OMIMno assertion criteria providedrisk factor
(Jan 1, 2007)
germlineliterature only

PubMed (9)
[See all records that cite these PMIDs]

Gordeeva, E. My Sergei--A Love Story. New York: Warner Books, Inc. 1996.

Summary from all submissions

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

Citations

PubMed

Gene frequencies of the five major human platelet antigens in African American, white, and Korean populations.

Kim HO, Jin Y, Kickler TS, Blakemore K, Kwon OH, Bray PF.

Transfusion. 1995 Oct;35(10):863-7.

PubMed [citation]
PMID:
7570918

A monoclonal antibody (SZ21) specific for platelet GPIIIa distinguishes P1A1 from P1A2.

Weiss EJ, Goldschmidt-Clermont PJ, Grigoryev D, Jin Y, Kickler TS, Bray PF.

Tissue Antigens. 1995 Nov;46(5):374-81.

PubMed [citation]
PMID:
8838346
See all PubMed Citations (9)

Details of each submission

From OMIM, SCV000034773.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (9)

Description

The molecular basis of the platelet-specific alloantigen system Pl(A) is a 1565T-C transition in exon 2 of the ITGB3 gene, resulting in a leu33-to-pro (L33P) substitution which corresponds to Pl(A1) and Pl(A2), respectively (Newman et al., 1989). Pl(A) is also known as alloantigen Zw.

Kim et al. (1995) determined the allelic frequencies of Pl(A1) and Pl(A2) in African Americans, whites, and Koreans living in the metropolitan Baltimore area.

Myocardial Infarction, Susceptibility to

Using a monoclonal antibody that specifically distinguished Pl(A1) from Pl(A2), Weiss et al. (1995) observed an unexpected high frequency of family members homozygous for the A2 allele in kindreds with a high prevalence of acute coronary events at a relatively young age (under 60 years). In a case-control study, Weiss et al. (1996) found that the A2 allele was 2.1 times more prevalent among 71 patients with myocardial infarction (see 608446) or unstable angina than among controls (39.4% vs 19.1%, respectively; P = 0.01). In a subgroup of patients whose disease began before the age of 60 years, the prevalence of the A2 allele was 50%, a value that was 3.6 times that among control subjects under 60 years of age (13.9%; P = 0.002), yielding an odds ratio (OR) of 2.8 for those with the A2 allele. In patients less than 60 years of age at the onset of disease, the OR was 6.2.

Goldschmidt-Clermont et al. (1996) reported without supporting data that the other major polymorphisms were not associated with myocardial infarction: Ko(a), Ko(b), Bak(a), Bak(b), Pen(a), Pen(b), Br(a), and Br(b).

Goldschmidt-Clermont et al. (1996) presented evidence that Sergei Grinkov, twice Olympic pairs figure skating gold medalist, was heterozygous for the A1/A2 polymorphism and suggested that this may have been related to his precocious coronary artery disease. Grinkov, aged 28, collapsed suddenly while training on the ice rink in Lake Placid, New York, and could not be resuscitated. Necropsy showed severe coronary artery disease and a recent (4- to 6-hour-old) anteroseptal myocardial infarction (MI). He had never sought medical attention for a heart problem. He was not a smoker, did not use drugs or medications, did not have hypertension or diabetes mellitus, his total cholesterol and lipid profiles were unremarkable, and he trained for several hours daily. Significantly, his father died suddenly at the age of 52 years. See the lay account by Grinkov's widow, Ekaterina Gordeeva (1996).

Goldschmidt-Clermont et al. (1999) genotyped 116 asymptomatic sibs (60 Caucasians, 56 Afro-Caribbeans) of patients with coronary heart disease manifested before the age of 60 years for the Pl(A) polymorphism. A control cohort consisted of 268 individuals (168 Caucasians, 100 Afro-Caribbeans) who were matched for race and geographic area but were free of coronary heart disease. The authors also characterized the sib cohort for other atherogenic and thrombogenic risk factors. The results supported the hypothesis that the prevalence of Pl(A2)-positive individuals is high in kindreds with premature coronary heart disease. Hence, like the established risk factors that tend to cluster in families with premature coronary heart disease and contribute strongly to the accelerated atherosclerotic process affecting these individuals, the Pl(A2) polymorphism of GP IIIa may represent an inherited risk that promotes the thromboembolic complications of coronary heart disease. That these asymptomatic sibs had overall less-established risk factors than their Pl(A1) counterparts may provide an explanation for why they remained asymptomatic despite their Pl(A2) positivity.

In a cross-sectional study of patients with a history of myocardial infarction and in matched controls from the Finnish population, Pastinen et al. (1998) analyzed common variants of 8 genes implicated previously as risk factors for coronary heart disease or MI. The most common low density lipoprotein receptor (LDLR; 606945) mutations in Finland were also included in the analysis. Multiplex genotyping of the target genes was performed using a specific and efficient array-based minisequencing system. The 4G allele of the PAI1 (173360) gene (P less than 0.05) and the Pl(A2) allele of the glycoprotein IIIa gene (P less than 0.01) were associated with an increased risk of MI in the Finnish study population. They found that the combined effect of these risk alleles conferred a high risk for the development of MI (OR = 4.5, P = 0.001), which was particularly prominent in male subjects (OR = 6.4, P = 0.0005). The observation of 2 separate genes contributing an additive risk of developing MI exemplified the advantages of multiplex analysis of genetic variation.

Undas et al. (2001) reported studies in healthy, male, nonsmoking medical students aged 21 to 24 years using a controlled method for producing microvascular injury. They found that the Pl(A2) variant was associated with enhanced thrombin generation and impaired antithrombotic action of aspirin at the site of microvascular injury.

Neonatal Alloimmune Thrombocytopenia and Posttransfusion Purpura

Pl(A) is the alloantigen most frequently implicated in syndromes of immune-mediated platelet destruction, particularly neonatal alloimmune thrombocytopenia and posttransfusion purpura (Newman et al., 1989).

Hip Fracture, Susceptibility to

Tofteng et al. (2007) analyzed the L33P polymorphism in 9,233 randomly selected Danish individuals, of whom 267 had a hip fracture (see 166710) during a 25-year follow-up period. Individuals homozygous for L33P had a 2-fold greater risk of hip fracture compared to noncarriers (p = 0.02), with risk confined primarily to postmenopausal women, in whom the hazard ratio was 2.6 after adjustment for age at menopause and use of hormone replacement therapy.

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

Last Updated: Mar 30, 2019

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