An intergenic region between the tagSNP rs3793917 and rs11200638 in the HTRA1 gene indicates association with age-related macular degeneration.
OBJECTIVE
There is still a debate as to whether the LOC387715 or HTRA1 genes represent the key significant association identified with age-related macular degeneration (AMD) on the long arm of chromosome 10, region 26.


METHODS
An Australian patient cohort was genotyped by using tagged single nucleotide polymorphisms (tSNPs) to identify a causal SNP within this region.


RESULTS
Multiple tSNPs across the region showed association with AMD with the tSNP rs3793917 (odds ratio [OR], 3.45; 95% confidence interval [CI], 2.36-5.05, P = 2.8 × 10(-13)) having the highest association with AMD. This tSNP occurred in the intergenic region between the LOC387715 and HTRA1 genes. A second tSNP rs2672587 (OR, 2.92; 95% CI, 2.04-4.17; P = 7.7 × 10(-11)) located in intron 1 of the HTRA1 gene had the second highest association with AMD. After logistic regression analysis, the only tSNP to survive covariate testing was rs3793917, which occurred in the same LD block as the HTRA1 promoter SNP rs11200638 (r(2) = 0.88, D' = 0.97).


CONCLUSIONS
The findings indicate that the intergenic region between the tSNP rs3793917 and the SNP rs11200638 in the HTRA1 gene is the most likely site explaining the significant association with AMD.
Richardson
Andrea J
AJ
Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, Victoria, Australia. andreajr@unimelb.edu.au
Islam
F M Amirul
FM
Aung
Khin Zaw
KZ
Guymer
Robyn H
RH
Baird
Paul N
PN
D000368:Aged; D020256:Choroidal Neovascularization / Q000235:genetics; D021901:DNA, Intergenic / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D057092:Geographic Atrophy / Q000235:genetics; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics*
D021901:DNA, Intergenic; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases