Assessment of the contribution of CFH and chromosome 10q26 AMD susceptibility loci in a Russian population isolate.
OBJECTIVE
A strong association has been confirmed between age-related macular degeneration (AMD) and variants at two independent loci including Tyr402His in the complement factor H (CFH) on 1q32 and Ser69Ala at LOC387715, a hypothetical gene on chromosome 10q26. The contribution of both loci to AMD was investigated in an isolated north-west Russian population.


METHODS
Together with a PLEKHA1 variant at 10q26, the CFH Tyr402His and LOC387715 Ser69Ala polymorphisms were genotyped in 155 patients with AMD and 151 age-matched controls. chi(2) and Mantel-Haenszel (M-H) score tests were used to test for association. Sex-adjusted ORs were calculated.


RESULTS
The frequency of the Tyr402His C allele was significantly higher in patients with AMD compared with controls (p(M-H)=0.0035). The increased risk observed in patients homozygous for the C allele (OR(HOM)=2.71, 95% CI 1.25 to 5.90) in this indigenous Russian population was considerably lower than that observed in previous western Caucasian populations. A significant increase in the frequency of the LOC387715 variant was observed in patients with late-stage AMD compared with controls (p(M-H)=0.007), with a homozygous OR of 3.47 (95% CI 1.01 to 11.9), although this association was not seen with early-stage AMD.


CONCLUSIONS
The CFH gene contributes to AMD in this Russian population, although the risk conferred is considerably lower in this population than that found in other Western populations. A contribution of LOC387715 to disease in this population is also likely to be of weak effect.
Fisher
Sheila A
SA
Department of Medical and Molecular Genetics, Guy's King's and St Thomas' School of Medicine, King's College, London, UK.
Rivera
Andrea
A
Fritsche
Lars G
LG
Babadjanova
Gulja
G
Petrov
Sergey
S
Weber
Bernhard H F
BH
D000368:Aged; D016022:Case-Control Studies; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D017242:Complement Factor H / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012426:Russia
D017242:Complement Factor H