Asp92Asn polymorphism in the myeloid IgA Fc receptor is associated with myocardial infarction in two disparate populations: CARE and WOSCOPS.
OBJECTIVE
Statins reduce inflammation and risk of myocardial infarction (MI). Because the myeloid IgA Fc receptor encoded by FCAR mediates inflammation, we hypothesized that the FCAR Asp92Asn polymorphism is associated with risk of MI and that this risk would be modified by pravastatin.


RESULTS
In the placebo arm of the Cholesterol and Recurrent Events (CARE) study, male carriers of the 92Asn allele had an adjusted hazard ratio for incident MI of 1.68 (95% CI 1.10 to 2.57); relative risk reduction by pravastatin was 69% in carriers and 12% in noncarriers (P(interaction)=0.007). In the placebo arm of the all-male West of Scotland Coronary Prevention Study (WOSCOPS), carriers had an adjusted odds ratio for incident coronary heart disease (CHD) of 1.46 (90% CI 1.05 to 2.03); for pravastatin compared with placebo treatment, the adjusted odds ratios were 0.55 (95% CI 0.32 to 0.93) in carriers and 0.65 (95% CI 0.51 to 0.83) in noncarriers (P(interaction)=0.55).


CONCLUSIONS
Carriers of 92Asn had increased risk of MI in CARE and increased odds of CHD in WOSCOPS. Pravastatin significantly reduced risk in carriers in both CARE and WOSCOPS. A genotype by treatment interaction was observed in CARE but not in WOSCOPS.
Iakoubova
Olga A
OA
Celera Inc, 1401 Harbor Bay Parkway, Alameda, CA 94502, USA. olga.iakoubova@celeradiagnostics.com
Tong
Carmen H
CH
Chokkalingam
Anand P
AP
Rowland
Charles M
CM
Kirchgessner
Todd G
TG
Louie
Judy Z
JZ
Ploughman
Lynn M
LM
Sabatine
Marc S
MS
Campos
Hannia
H
Catanese
Joseph J
JJ
Leong
Diane U
DU
Young
Bradford A
BA
Lew
David
D
Tsuchihashi
Zenta
Z
Luke
May M
MM
Packard
Christopher J
CJ
Zerba
Kim E
KE
Shaw
Peter M
PM
Shepherd
James
J
Devlin
James J
JJ
Sacks
Frank M
FM
D000483:Alleles; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D015703:Antigens, CD / Q000235:genetics*; D001216:Asparagine / Q000235:genetics*; D001224:Aspartic Acid / Q000235:genetics*; D003327:Coronary Disease / Q000209:etiology / Q000235:genetics / Q000517:prevention & control; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology / Q000235:genetics* / Q000517:prevention & control; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017035:Pravastatin / Q000627:therapeutic use; D011961:Receptors, Fc / Q000235:genetics*; D012307:Risk Factors; D012606:Scotland
D000924:Anticholesteremic Agents; D015703:Antigens, CD; C036832:Fc(alpha) receptor; D011961:Receptors, Fc; D001224:Aspartic Acid; D001216:Asparagine; D017035:Pravastatin