Rs11200638

From SNPedia

rs11200638, a SNP in the HTRA1 promoter, is associated with a 10 fold increased risk of wet age related macular degeneration in Japanese [PMID 17053108] and Caucasian [PMID 17053109] populations. Further confirmed [PMID 18207215, PMID 18206206]. The genotype at highest risk is (A;A).

Note that this SNP is completely predictive (ie is in perfect linkage disequilibrium) with rs10490924, thus the status of one predicts the status of the other.

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

[PMID 17884985] show that rs11200638 has no significant impact on HTRA1 promoter activity in three different cell lines, and HTRA1 mRNA expression exhibits no significant change between control and AMD retinas

[PMID 18301036] A study of 95 Taiwanese Chinese confirms rs11200638(A) allele risk for both wet and dry forms of AMD, with heterozygote odds ratio of 1.97 [CI:0.81-4.81], homozygote OR = 8.59 [CI: 3.28-22.49], p=6.7x10^-3 for an additive allele-dosage model.

[PMID 18316707] A study of Chinese AMD patients reports a 7.6x increased risk for rs11200638(A), and finds that smoking almost doubles the risk, to 15.7x increased risk. Carriers of both rs11200638 and rs800292 risk alleles pushes the odds ratio up to 23x. Overall, an "extremely high" population attributable risk (PAR) of 78% reported for these SNPs.

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

[PMID 18316707]

• rs11200638 1.7x10-14 (-625G>A)is the most significant associated SNP with a high OR of 7.6 (95%CI: 3.94-14.51)
• rs2672598 3.0x10-10 (-487T>C)
• rs1049331 3.7x10-12 (102C>T, Ala34Ala)
• rs2293870 3.7x10-12 (108G>T, Gly36Gly)
• haplotype ACCTT, significantly predisposes to AMD (p= 6.68x10-14)
• smoking and rs800292 (184G>A, Val62Ile) of CFH.
• The combined OR for disease of smoking and rs11200638 (HTRA1) caused a 15.7 fold increased risk
• The combined OR for rs800292 and rs11200638 showed a 23.3 fold increased risk
• An extremely high population attributable risk (PAR) of 78% was also found.

[PMID 19026638] A meta-analysis of 14 case-control studies published prior to Sept. 2008 concluded that rs11200638 probably increases the risk of wet AMD in all populations.

GWAS
SNP	rs11200638
PubMedID	[PMID 17053108]
Condition	Wet age-related macular degeneration
Gene	HTRA1
Risk Allele	A
pValue	8.00E-012
OR	1.6
95% CI	0.71-3.61

[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 19798546] Association of HTRA1 promoter polymorphism with spinal disc degeneration in Japanese women

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

[PMID 20132989] Phenotype and Genotype Characteristics of Age-related Macular Degeneration in a Japanese Population