Complement factor h polymorphism, inflammatory mediators, and retinal vessel diameters: the rotterdam study.
OBJECTIVE
Retinal venular dilatation is associated with systemic inflammation. The hypothesis for the current study was that larger retinal venular diameters are related to the His allele of the Tyr402His polymorphism in the complement factor H (CFH) gene, a major inhibitor of the complement pathway. Possible effect modification by smoking and inflammatory markers was examined.


METHODS
This cross-sectional study was performed within the Rotterdam Study, a population-based study among elderly persons aged 55 years and older. The Tyr402His polymorphism of the CFH gene was genotyped in 5066 participants and retinal arteriolar and venular diameters were graded on digitized fundus transparencies.


RESULTS
Genotype frequencies were 41% in TyrTyr, 45% in TyrHis, and 14% in HisHis carriers. The His(402) allele was associated with smaller rather than larger venular diameters (age- and sex-adjusted means and standard errors [in micrometers] were 222.5 +/- 0.45 for TyrTyr, 221.9 +/- 0.43 for TyrHis, and 220.6 +/- 0.78 for HisHis carriers; P-trend = 0.03). This association was apparent only in never-smokers and was not modified by the inflammatory markers erythrocyte sedimentation rate, leukocyte count, C-reactive protein, or fibrinogen. Adjustment for cardiovascular risk factors did not change results. No associations were found with arteriolar diameters.


CONCLUSIONS
The findings do not support the hypothesis that the His(402) allele is related to larger retinal venular diameters. The association with smaller retinal venular diameters most likely is a chance finding, because it was present only among never-smokers and was not modified by inflammatory mediators of complement. These results suggest that the Tyr402His variant is not related to retinal venular diameters.
de Jong
Frank Jan
FJ
Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, The Netherlands.
Ikram
M Kamran
MK
Despriet
Dominiek D G
DD
Uitterlinden
André G
AG
Hofman
Albert
A
Breteler
Monique M B
MM
de Jong
Paulus T V M
PT
D000368:Aged; D000483:Alleles; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000378:metabolism; D017242:Complement Factor H / Q000235:genetics; D003430:Cross-Sectional Studies; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005838:Genotype; D006639:Histidine / Q000235:genetics; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012171:Retinal Vessels / Q000473:pathology*; D012907:Smoking; D014664:Vasodilation
C493495:CFH protein, human; D018836:Inflammation Mediators; D006639:Histidine; D017242:Complement Factor H; D005340:Fibrinogen; D002097:C-Reactive Protein