{{Rsnum
|rsid=11200638
|Gene=HTRA1
|Chromosome=10
|position=122461028
|Orientation=plus
|GMAF=0.2865
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(A;A)
|geno2=(A;G)
|geno3=(G;G)
|Gene_s=HTRA1
}}[[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.

A 2011 meta-analysis concluded that [[rs11200638]](A;G) and (A;A) carriers had 2.243 and 8.669 times the risk of developing AMD, respectively, when compared with those who carry the (G;G) genotype.{{PMID|21031019|OA=1
}}

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

{{PMID|17884985|OA=1
}} 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<sup>-3</sup> for an additive allele-dosage model.

{{PMID|18316707|OA=1
}} 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|OA=1
}} An analysis of the joint effects of [[rs1061170]], [[rs11200638]] and [[rs10490924]] on [[AMD]]

{{ neighbor
| rsid = 10490924
| distance = 6096
}}
{{ neighbor
| rsid = 2293870
| distance = 732
}}

{{PMID|18316707|OA=1
}} 
*[[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.

{{ neighbor
| rsid = 2672598
| distance = 138
}}
{{GWAS Summary
|SNP=rs11200638
|PubMedID=17053108
|Condition=Wet age-related macular degeneration
|Gene=HTRA1
|Risk Allele=A
|pValue=8.00E-012
|OR=1.6
|95CI=0.71-3.61
}}
{{PMID Auto
|PMID=19259132
|Title=Multilocus analysis of age-related macular degeneration.
|OA=1
}}
{{PMID Auto
|PMID=19255159
|Title=Age-Related Macular Degeneration Associated ARMS2 is not a Mitochondrial but Cytosolic Protein.
|OA=1
}}

{{omim
|desc=LOC387715 GENE
|id=611313
|rsnum=11200638
}}

{{omim
|desc=MACULAR DEGENERATION, AGE-RELATED, 7; ARMD7
|id=610149
|rsnum=11200638
}}

{{omim
|id=602194
|desc=HTRA SERINE PEPTIDASE 1; HTRA1
|rsnum=11200638
}}
{{PMID Auto
|PMID=19680273
|Title=ARMS2/HTRA1 and CFH polymorphisms are not associated with choroidal neovascularization in highly myopic eyes of the elderly Japanese population
}}
{{PMID Auto
|PMID=19798546
|Title=Association of HTRA1 promoter polymorphism with spinal disc degeneration in Japanese women
}}
{{PMID Auto
|PMID=19796758
|Title=Comprehensive Analysis of Complement Factor H and LOC387715/ARMS2/HTRA1 Variants with Respect to Phenotype in Advanced Age-related Macular Degeneration
|OA=1
}}
{{PMID Auto
|PMID=19491722
|Title=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 Auto
|PMID=19933195
|Title=Analysis of six genetic risk factors highly associated with AMD in the region surrounding ARMS2 and HTRA1 on chromosome 10q26
}}

{{PharmGKB
|RSID=rs11200638
|Name_s=
|Gene_s=HTRA1
|Feature=
|Evidence=PubMed ID:17053108; Web Resource:http://www.genome.gov/gwastudies/
|Annotation=GWAS Results: HTRA1 promoter polymorphism in wet age-related macular degeneration (Initial Sample Size: 96 Southeast Asian cases, 130 Southeast Asian controls; Replication Sample Size: NR; Risk Allele: rs11200638-A).
|Drugs=
|Drug Classes=
|Diseases=Macular Degeneration
|Curation Level=Non-Curated
|PharmGKB Accession ID=PA162356594
}}

{{PMID Auto
|PMID=20132989
|Title=Phenotype and Genotype Characteristics of Age-related Macular Degeneration in a Japanese Population
}}

{{PMID Auto
|PMID=20678803
|Title=Complement Factor H and High-Temperature Requirement A-1 Genotypes and Treatment Response of Age-related Macular Degeneration
}}

{{PharmGKB
|RSID=rs11200638
|Name_s=
|Gene_s=HTRA1
|Feature=
|Evidence=PubMed ID:17053109
|Annotation=The A allele of rs11200638, a SNP in the promoter region of HTRA1, was found to be significantly associated with increased risk for Age-related Macular degeneration in a Caucasian (White) case-control study.
|Drugs=
|Drug Classes=
|Diseases=Macular Degeneration
|Curation Level=Curated
|PharmGKB Accession ID=PA161889388
}}
{{PMID Auto
|PMID=21067572
|Title=Association Analysis of Nine Candidate Gene Polymorphisms in Indian Patients with Type 2 Diabetic Retinopathy
|OA=1
}}
{{PMID Auto
|PMID=21191724
|Title=Haplotype analysis of the ARMS2/HTRA1 region in Japanese patients with typical neovascular age-related macular degeneration or polypoidal choroidal vasculopathy
}}

{{omim
|id=602194
|rsnum=11200638
|variant=0001
}}

{{PMID Auto
|PMID=21878851
|Title=ASSOCIATION BETWEEN HIGH-RISK DISEASE LOCI AND RESPONSE TO ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT FOR WET AGE-RELATED MACULAR DEGENERATION
}}

{{PMID Auto
|PMID=21913742
|Title=Genetic predictors of response to photodynamictherapy
}}

{{PMID Auto
|PMID=22509112
|Title=Genetic associations in polypoidal choroidal vasculopathy: A systematic review and meta-analysis
|OA=1
}}

{{PMID Auto
|PMID=21959923
|Title=Association of ARMS2/HTRA1 variants with polypoidal choroidal vasculopathy phenotype in a Korean population
}}

{{PMID Auto
|PMID=22594510
|Title=Association of genetic polymorphisms with response to bevacizumab for neovascular age-related macular degeneration in the Chinese population
}}

{{PMID Auto
|PMID=22699975
|Title=Genetic analysis of simultaneous geographic atrophy and choroidal neovascularization
|OA=1
}}

{{PMID Auto
|PMID=22259222
|Title=Chlamydia infection status, genotype, and age-related macular degeneration
|OA=1
}}

{{PMID Auto
|PMID=17327825
|Title=An update on the genetics of age-related macular degeneration.
|OA=1
}}

{{PMID Auto
|PMID=17426452
|Title=HTRA1 variant confers similar risks to geographic atrophy and neovascular age-related macular degeneration.
}}

{{PMID Auto
|PMID=17438519
|Title=HTRA1 promoter polymorphism predisposes Japanese to age-related macular degeneration.
|OA=1
}}

{{PMID Auto
|PMID=17568988
|Title=Association of the HTRA1 gene variant with age-related macular degeneration in the Japanese population.
}}

{{PMID Auto
|PMID=17692272
|Title=LOC387715/HTRA1 variants in polypoidal choroidal vasculopathy and age-related macular degeneration in a Japanese population.
}}

{{PMID Auto
|PMID=17904186
|Title=HTRA1 variant increases risk to neovascular age-related macular degeneration in Chinese population.
}}

{{PMID Auto
|PMID=17917691
|Title=Genetic markers and biomarkers for age-related macular degeneration.
|OA=1
}}

{{PMID Auto
|PMID=18079691
|Title=PLEKHA1-LOC387715-HTRA1 polymorphisms and exudative age-related macular degeneration in the French population.
}}

{{PMID Auto
|PMID=18162041
|Title=Neovascular age-related macular degeneration risk based on CFH, LOC387715/HTRA1, and smoking.
|OA=1
}}

{{PMID Auto
|PMID=18362109
|Title=Genotype-phenotype correlations for exudative age-related macular degeneration associated with homozygous HTRA1 and CFH genotypes.
}}

{{PMID Auto
|PMID=18427598
|Title=Human HtrA1 in the archived eyes with age-related macular degeneration.
|OA=1
}}

{{PMID Auto
|PMID=18436811
|Title=Variants in the 10q26 gene cluster (LOC387715 and HTRA1) exhibit enhanced risk of age-related macular degeneration along with CFH in Indian patients.
}}

{{PMID Auto
|PMID=18515590
|Title=Association analysis of CFH, C2, BF, and HTRA1 gene polymorphisms in Chinese patients with polypoidal choroidal vasculopathy.
}}

{{PMID Auto
|PMID=18535016
|Title=Rhesus monkeys and humans share common susceptibility genes for age-related macular disease.
|OA=1
}}

{{PMID Auto
|PMID=18682812
|Title=Association of CFH, LOC387715, and HTRA1 polymorphisms with exudative age-related macular degeneration in a northern Chinese population.
|OA=1
}}

{{PMID Auto
|PMID=18718667
|Title=The HtrA1 promoter polymorphism, smoking, and age-related macular degeneration in multiple case-control samples.
|OA=1
}}

{{PMID Auto
|PMID=18939352
|Title=Correlation between CFH Y402H and HTRA1 rs11200638 genotype to typical exudative age-related macular degeneration and polypoidal choroidal vasculopathy phenotype in the Japanese population.
}}

{{PMID Auto
|PMID=19026761
|Title=Molecular pathology of age-related macular degeneration.
|OA=1
}}

{{PMID Auto
|PMID=19048105
|Title=Multifactor effects and evidence of potential interaction between complement factor H Y402H and LOC387715 A69S in age-related macular degeneration.
|OA=1
}}

{{PMID Auto
|PMID=19065273
|Title=Sequence variants in HTRA1 and LOC387715/ARMS2 and phenotype and response to photodynamic therapy in neovascular age-related macular degeneration in populations from Israel.
|OA=1
}}

{{PMID Auto
|PMID=19169232
|Title=Variations in five genes and the severity of age-related macular degeneration: results from the Muenster aging and retina study.
}}

{{PMID Auto
|PMID=19187590
|Title=Genetic variants in three genes and smoking show strong associations with susceptibility to exudative age-related macular degeneration in a Chinese population.
}}

{{PMID Auto
|PMID=19202148
|Title=Assessing susceptibility to age-related macular degeneration with proteomic and genomic biomarkers.
|OA=1
}}

{{PMID Auto
|PMID=19628747
|Title=Toll-like receptor polymorphisms and age-related macular degeneration: replication in three case-control samples.
|OA=1
}}

{{PMID Auto
|PMID=19845562
|Title=Analysis of complement factor H Y402H, LOC387715, HTRA1 polymorphisms and ApoE alleles with susceptibility to age-related macular degeneration in Hungarian patients.
}}

{{PMID Auto
|PMID=19933189
|Title=Compound heterozygosity of two novel truncation mutations in RP1 causing autosomal recessive retinitis pigmentosa.
}}

{{PMID Auto
|PMID=20140183
|Title=Genetic and functional dissection of HTRA1 and LOC387715 in age-related macular degeneration.
|OA=1
}}

{{PMID Auto
|PMID=20157352
|Title=Genetic analysis of typical wet-type age-related macular degeneration and polypoidal choroidal vasculopathy in Japanese population.
|OA=1
}}

{{PMID Auto
|PMID=20161815
|Title=SERPING1 polymorphisms in polypoidal choroidal vasculopathy.
|OA=1
}}

{{PMID Auto
|PMID=20445115
|Title=An intergenic region between the tagSNP rs3793917 and rs11200638 in the HTRA1 gene indicates association with age-related macular degeneration.
}}

{{PMID Auto
|PMID=20456446
|Title=LOC387715/HTRA1 polymorphisms, smoking and combined effects on exudative age-related macular degeneration in a Korean population.
}}

{{PMID Auto
|PMID=20664794
|Title=Age-related macular degeneration-associated variants at chromosome 10q26 do not significantly alter ARMS2 and HTRA1 transcript levels in the human retina.
|OA=1
}}

{{PMID Auto
|PMID=20689796
|Title=Monozygotic twins with polypoidal choroidal vasuculopathy.
|OA=1
}}

{{PMID Auto
|PMID=20881291
|Title=Persons with age-related maculopathy risk genotypes and clinically normal eyes have reduced mesopic vision.
|OA=1
}}

{{PMID Auto
|PMID=21203342
|Title=Elevated C-reactive protein levels and ARMS2/HTRA1 gene variants in subjects without age-related macular degeneration.
|OA=1
}}

{{PMID Auto
|PMID=21558292
|Title=CFH, VEGF and HTRA1 promoter genotype may influence the response to intravitreal ranibizumab therapy for neovascular age-related macular degeneration.
}}

{{PMID Auto
|PMID=21609242
|Title=Age-related macular degeneration-susceptibility single nucleotide polymorphisms in a han chinese control population.
}}

{{PMID Auto
|PMID=22491416
|Title=Differentiation of exudative age-related macular degeneration and polypoidal choroidal vasculopathy in the ARMS2/HTRA1 locus.
}}

{{PMID Auto
|PMID=22618592
|Title=Association of genetic polymorphisms and age-related macular degeneration in chinese population.
}}

{{GET Evidence
|impact=pathogenic
|qualified_impact=Insufficiently evaluated pathogenic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs11200638
|overall_frequency_n=16
|overall_frequency_d=82
|overall_frequency=0.195122
|n_genomes=11
|n_genomes_annotated=0
|n_haplomes=13
|n_articles=1
|n_articles_annotated=0
|in_gwas=Y
|in_pharmgkb=Y
|autoscore=2
|webscore=N
}}

{{PMID Auto
|PMID=23337555
|Title=Pharmacogenetics for Genes Associated with Age-Related Macular Degeneration in the Comparison of AMD Treatments Trials (CATT)
|OA=1
}}

{{PMID Auto
|PMID=23582991
|Title=Genetic Influences on the Outcome of Anti-Vascular Endothelial Growth Factor Treatment in Neovascular Age-related Macular Degeneration
}}

{{PMID Auto
|PMID=23644223
|Title=Variants at chromosome 10q26 locus and the expression of HTRA1 in the retina
}}

{{PMID Auto
|PMID=24080590
|Title=Genetic Association with Response to Intravitreal Ranibizumab for Neovascular Age-Related Macular Degeneration in the Han Chinese Population
}}

{{PMID Auto
|PMID=24393350
|Title=Genes in the High-Density Lipoprotein Metabolic Pathway in Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy
}}

{{PMID Auto
|PMID=22556410
|Title=Detrimental role for human high temperature requirement serine protease A1 (HTRA1) in the pathogenesis of intervertebral disc (IVD) degeneration.
|OA=1
}}

{{PMID Auto
|PMID=23204795
|Title=Pharmacogenetic influence of LOC387715/HTRA1 on the efficacy of bevacizumab treatment for age-related macular degeneration in a Korean population.
|OA=1
}}

{{PMID Auto
|PMID=24865190
|Title=Association of Specific Genetic Polymorphisms with Age-related Macular Degeneration in a Northern Chinese Population
}}
{{on chip | 23andMe v2}}