Relationship between age-related macular degeneration-associated variants of complement factor H and LOC387715 with coronary artery disease.
OBJECTIVE
To determine whether either of the gene variants associated with age-related macular degeneration is associated with coronary artery disease (CAD).


METHODS
This study consisted of 493 patients who underwent clinically indicated coronary angiography between June 1, 1998, and January 1, 1999. The Y402H variant of the complement factor H (CFH) gene and the A69S variant of the LOC387715 gene locus were examined by restriction fragment length polymorphism. Multiple logistic regression models were used to assess the association of CFH and LOC gene variants with CAD. Covariates with well-established associations with CAD were also evaluated.


RESULTS
Seventy patients (14%) were homozygous for the histidine variant (HH) of CFH, 237 (48%) were heterozygous for the histidine variant (HY), and 186 (38%) were homozygous for the tyrosine variant (YY). Three hundred eight patients (62%) were homozygous for the alanine allele of LOC387715, 170 (34%) were heterozygous for Ala and Ser alleles, and 15 (3%) were homozygous for the serine variant. The overall association of the CFH genotype with CAD was not statistically significant (P=.08). However, some evidence (P=-.046) suggested that CAD was increased for the HH genotype compared to the homozygous wild-type YY genotype (odds ratio, 1.95; 95% confidence interval, 1.01-3.76). Male sex, hypertension, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and age were other variables that demonstrated significant associations with CAD. The overall effect of the LOC genotype was not statistically significant (P=-.06). Heterozygosity for the serine variant was (P=-.02) associated with the absence of CAD vs the AS genotype (odds ratio, 0.59; confidence interval, 0.38-0.91; P=-.02).


CONCLUSIONS
The CFH genotype may have an independent association with CAD, although our evidence did not show statistical significance. Controlling for known risk factors, the age-related macular degeneration-associated HH variant appears to be associated with CAD. The LOC387715 gene may also play a role in CAD.
Pulido
Jose S
JS
Department of Ophthalmology, Mayo Clinic College of Medicine, Rochester, Minn 55905, USA.
McConnell
Joseph P
JP
Lennon
Ryan J
RJ
Bryant
Sandra C
SC
Peterson
Lisa M
LM
Berger
Peter B
PB
Somers
Virend
V
Highsmith
W Edward
WE
D000328:Adult; D000367:Age Factors; D000368:Aged; D000483:Alleles; D016009:Chi-Square Distribution; D017242:Complement Factor H / Q000235:genetics*; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008268:Macular Degeneration / Q000235:genetics*; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
D017242:Complement Factor H