Analysis of CFH, TLR4, and APOE polymorphism in India suggests the Tyr402His variant of CFH to be a global marker for age-related macular degeneration.
OBJECTIVE
To screen polymorphisms in complement factor-H (CFH), toll-like receptor 4 (TLR4), and APOE genes as potential risk factors for age-related macular degeneration (AMD) in Indian patients.


METHODS
One hundred patients with AMD and 120 normal control subjects were screened for the polymorphisms by restriction digestion and resequencing. Five intragenic SNPs in CFH were screened to generate haplotype data in cases and controls. The data were analyzed in conjunction with data from other populations based on genotype and haplotype frequencies, and odds ratios were computed to estimate the risk of AMD in the different genotypes.


RESULTS
Significant association was noted with the CFH variant (Tyr402His) among AMD cases (P = 1.19 x 10(-7)). Individuals homozygous for the mutant genotype CC had a significantly higher risk (P < 0.0001) of AMD (OR = 11.52; 95% CI 5.05-26.28) than those carrying a single copy of the C allele (OR = 1.51; 95% CI 0.82-2.80), after adjusting for age, gender, and diabetes. Linkage disequilibrium and haplotype analysis at the CFH locus indicated the C-G-T-C-A-G to be a risk haplotype (P = 0.0003). No significant differences were observed in the genotype frequencies of APOE polymorphisms among patients and control subjects (P = 0.76). The carriers of epsilon4 allele had a reduced risk (P = 0.03) of AMD (OR = 0.42, 95% CI 0.19-0.91). TLR4 did not exhibit any association with AMD.


CONCLUSIONS
The CFH polymorphism Tyr402His appears indicative of AMD pathogenesis. Diabetes, age, and gender in the presence of the homozygous "CC" genotype in CFH carry an increased risk of AMD. Hence this polymorphism could be used as a potential marker for predictive testing across continents.
Kaur
Inderjeet
I
Kallam Anji Reddy Molecular Genetics Laboratory, Hyderabad, India.
Hussain
Avid
A
Hussain
Nazimul
N
Das
Taraprasad
T
Pathangay
Avinash
A
Mathai
Annie
A
Hussain
Anjli
A
Nutheti
Rishita
R
Nirmalan
Praveen K
PK
Chakrabarti
Subhabrata
S
D000368:Aged; D001057:Apolipoproteins E / Q000235:genetics*; D017242:Complement Factor H / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007194:India; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D051197:Toll-Like Receptor 4 / Q000235:genetics*
D001057:Apolipoproteins E; C493495:CFH protein, human; D005819:Genetic Markers; D051197:Toll-Like Receptor 4; D017242:Complement Factor H