The poliovirus receptor related 2 (PRR2) and apolipoprotein E genes and coronary heart disease.
BACKGROUND
Recently, we localized the Human Poliovirus Receptor Related 2 Gene (PRR2) 17kb centromeric to the gene for apolipoprotein E (APOE). Common polymorphisms in the latter have been found, in some studies, to be related to coronary heart disease (CHD) but the PRR2 gene has not been studied in this context. Here, we examined relationships between a PRR2 Sau96I (A/G) polymorphism, the epsilon2, 3 and 4 alleles of APOE and CHD.


METHODS
Consecutive Caucasian patients (n = 640) < 50 years with angiographically documented coronary obstructive disease and/or with unequivocal myocardial infarction were compared with 624 control subjects, aged 30-50 years, randomly selected from the community and without a history of CHD.


RESULTS
An excess of PRR2-A homozygotes was observed in cases (20% vs. 15%; OR 1.4, CI 1.04-1.86, P = 0.026) particularly in those with single vessel disease (OR 1.7, CI 1.2-2.4, P <0.01). The A allele was in linkage disequilibrium with the epsilon4 allele and the G allele with the epsilon2. Overrepresentation of the A allele and underrepresentation of the G allele in the CHD group did not reach significance (P = 0.054). While the epsilon2 allele was underrepresented in the CHD group (OR 0.64, CI 0.46-0.89, P = 0.009), the epsilon4 allele was not significantly overrepresented.


CONCLUSIONS
The relationship between the PRR2 Sau96I (A/G) polymorphism and early onset coronary artery disease may be due to linkage disequilibrium with the APOE gene and underrepresentation, or a protective effect, of the epsilon2 allele. Alternatively, since A allele homozygosity is particularly overrepresented, the relationship could be more direct, perhaps through a viral association.
Freitas
Elizabeth M
EM
Department of Clinical Immunology, Royal Perth Hospital, Western Australia, Australia.
Phan
Tony C A
TC
Herbison
Carly E
CE
Christiansen
Frank T
FT
Taylor
Roger R
RR
Van Bockxmeer
Frank M
FM
D000328:Adult; D001057:Apolipoproteins E / Q000235:genetics*; D015815:Cell Adhesion Molecules; D017023:Coronary Angiography; D003327:Coronary Disease / Q000000981:diagnostic imaging / Q000209:etiology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D000075983:Nectins; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus; D012307:Risk Factors
D001057:Apolipoproteins E; D015815:Cell Adhesion Molecules; D008562:Membrane Glycoproteins; D000075983:Nectins; D018124:Receptors, Tumor Necrosis Factor; D053240:Receptors, Tumor Necrosis Factor, Member 14; D011991:Receptors, Virus; C506028:TNFRSF14 protein, human