Rs10490924

This SNP has been recognized by the Coriell Personalized Medicine Collaborative ICOB. Additional information is available here

rs10490924 was identified as a risk factor from chromosome 10 related to age related macular degeneration. The risk allele is (T). Odds ratios for heterozygotes and homozygotes are, respectively, 2.69 (CI: 2.22-3.27) and 8.21 (CI: 5.79-11.65).[PMID 16174643]

Disease risk in combination with the rs1061170 SNP in the CFH gene is dramatically increased. Homozygotes for both the rare/risk alleles at both loci are estimated to be at 57 fold higher risk for age related macular degeneration than individuals homozygous for the common alleles at both loci. [PMID 16174643]

A subsequent study indicated that the risk based on solely the ARMS2 SNP rs10490924 is significantly higher in smokers than in non-smokers. [PMID 16642439]

Based on a study of ~750 patients, rs10490924 is significantly higher in participants with choroidal neovascularization than in those with geographic atrophy (odds ratio 1.37, CI: 1.21-1.54, p = 4.2 × 10(-7)).[PMID 21122828]

Note that this SNP is completely predictive (ie is in perfect linkage disequilibrium) with rs11200638, thus the status of one predicts the status of the other.

[PMID 17884985] A likely biological mechanism is that the A69S change in the LOC387715/ARMS2 protein affects its presumptive function in mitochondria.

[PMID 18164066] rs10490924 and rs11200638 defined 2 significant haplotypes associated with increased risk of neovascular AMD.

[PMID 18400199] In comparison with wild-type homozygosity (G;G), homozygosity for the at-risk allele genotype (T;T) increased the likelihood for polypoidal choroidal vasculopathy (PCV) 8.4-fold (CI: 3.6-19.5) and heterozygosity for the at-risk allele genotype (G;T) increased the risk for PCV 4x (CI: 1.9-8.4), based on a study of ~100 Japanese patients.

[PMID 18682806] An analysis of the joint effects of rs1061170, rs11200638 and rs10490924 on AMD

[PMID 19268887] ARMS2 (LOC387715) Variants in Japanese Patients with Exudative Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy.

[PMID 19259132] Multilocus analysis of age-related macular degeneration.

[PMID 19255159] Age-Related Macular Degeneration Associated ARMS2 is not a Mitochondrial but Cytosolic Protein.

[PMID 19680273] ARMS2/HTRA1 and CFH polymorphisms are not associated with choroidal neovascularization in highly myopic eyes of the elderly Japanese population

[PMID 19797206] Susceptibility genes and progression in age-related maculopathy - a study of single eyes. The prospective Muenster Ageing and Retina Study (MARS)

[PMID 19796758] Comprehensive Analysis of Complement Factor H and LOC387715/ARMS2/HTRA1 Variants with Respect to Phenotype in Advanced Age-related Macular Degeneration

[PMID 19491722] Analyses of single nucleotide polymorphisms and haplotype linkage of LOC387715 and the HTRA1 gene in exudative age-related macular degeneration in a Chinese cohort

[PMID 19898184] Angiographic lesion size associated with loc387715 a69s genotype in subfoveal polypoidal choroidal vasculopathy

[PMID 19933195] Analysis of six genetic risk factors highly associated with AMD in the region surrounding ARMS2 and HTRA1 on chromosome 10q26

[PMID 20157352] Genetic analysis of typical wet-type age-related macular degeneration and polypoidal choroidal vasculopathy in Japanese population

[PMID 20182747] Analysis of the indel at the ARMS2 3'UTR in age-related macular degeneration

[PMID 20381870] Progression of Geographic Atrophy and Genotype in Age-Related Macular Degeneration

GWAS snp
PMID	[PMID 20385826]
Trait	Age-related macular degeneration
Title	Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC)
Risk Allele
P-val	5E-119
Odds Ratio	None None

[PMID 20664795] R102G polymorphism of the C3 gene associated with exudative age-related macular degeneration in a French population

[PMID 20688737] Joint Effect of Cigarette Smoking, CFH and LOC387715/HTRA1 Polymorphisms on Polypoidal Choroidal Vasculopathy

GWAS snp
PMID	[PMID 20861866]
Trait
Title	Genome-wide association identifies SKIV2L and MYRIP as protective factors for age-related macular degeneration
Risk Allele	T
P-val	1E-60
Odds Ratio	2.75 [NR]

[PMID 21067572] Association Analysis of Nine Candidate Gene Polymorphisms in Indian Patients with Type 2 Diabetic Retinopathy

[PMID 21621535] No association between the T280M polymorphism of the CX3CR1 gene and exudative AMD

GWAS snp
PMID	[PMID 21665990]
Trait
Title	Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration.
Risk Allele	T
P-val	0
Odds Ratio	2.9400 [NR]

[PMID 21825189] Complement Factor H 402H Variant and Reticular Macular Disease

[PMID 21878851] ASSOCIATION BETWEEN HIGH-RISK DISEASE LOCI AND RESPONSE TO ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT FOR WET AGE-RELATED MACULAR DEGENERATION

[PMID 21882634] [Influence of genetic mutations on clinical presentation of subretinal neovascularization. Report 2: The impact of HTRA and VEGF genes polymorphism]

[PMID 22049084] HTRA1 regulates angiogenesis through TGF-? family member GDF6

[PMID 22509112] Genetic associations in polypoidal choroidal vasculopathy: A systematic review and meta-analysis

[PMID 22552255] Retinal function and CFH-ARMS2 polymorphisms analysis: a pilot study in Italian AMD patients

[PMID 21959923] Association of ARMS2/HTRA1 variants with polypoidal choroidal vasculopathy phenotype in a Korean population