{{Rsnum
|rsid=3825942
|Gene=LOXL1
|Chromosome=15
|position=73927241
|Orientation=plus
|ReferenceAllele=G
|MissenseAllele=A
|GMAF=0.225
|Gene_s=LOXL1,RNASEH2B
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(C;C)
|geno2=(C;T)
|geno3=(T;T)
}}{{ population diversity
| geno1=(C;C)
| geno2=(C;T)
| geno3=(T;T)
| CEU | 68.3 | 31.7 | 0.0
| HCB | 71.6 | 26.9 | 1.5
| JPT | 77.3 | 20.5 | 2.3
| YRI | 33.9 | 51.6 | 14.5
| ASW | 37.5 | 44.6 | 17.9
| CHB | 71.6 | 26.9 | 1.5
| CHD | 69.2 | 29.8 | 1.0
| GIH | 63.0 | 31.0 | 6.0
| LWK | 33.0 | 48.1 | 18.9
| MEX | 61.8 | 34.5 | 3.6
| MKK | 43.0 | 43.6 | 13.4
| TSI | 63.3 | 34.7 | 2.0
| HapMapRevision=28
}}[[rs3825942]], also known as G153D, a SNP causing an amino acid change in the lysyl oxidase 1 [[LOXL1]] gene, has been linked to exfoliation [[glaucoma]] (also known as exfoliation syndrome). This form of glaucoma causes up to 10% of the cases of blindness in many countries, including the US. {{PMID|17690259}} From the abstract of this study: "Approximately 25% of the general population is homozygous for the highest risk haplotype [C;C here combined with other risk SNPs] and their risk of suffering XFG (exfoliation glaucoma) is over 100 times that of those only carrying low-risk haplotypes."

The risk allele for this SNP is [[rs3825942]](C), as oriented with respect to the dbSNP entry, and it confers a estimated relative risk (by itself) of 27 compared to the (T) allele. The odds ratio is 20.10 (CI 10.80-37.41). [Note that the (C) allele is actually quite common in most European populations.]

A meta-analysis including 24 articles across 5 ethnicities (Caucasian, African, Japanese, Indian, and Chinese) concluded that [[rs3825942]] is the common disease-associated SNP in all populations, whereas [[rs1048661]] and [[rs2165241]] were inconsistent. The odds ratio is approximately 10 for [[rs3825942]](C;C), while the heterozygote [[rs3825942]](C;T) was not statistically significant. [[rs3825942]] was not associated with primary open angle glaucoma (POAG).{{PMID|20142848|OA=1
}}

With so many people at high risk, shouldn't the number of cases be much higher? Not necessarily, since glaucoma risk only becomes high in [[ageing|older individuals]]. [To put it another way: plenty of folks don't live long enough to find out if they would have gotten glaucoma.] The estimate for glaucoma incidence worldwide is 10-20% only for individuals over 60 years of age; in Iceland, where glaucoma incidence is high, 40% of individuals 80 or older show signs of exfoliation ''syndrome'', which has been seen to convert to exfolation ''glaucoma'' at a rate of 60% - over a 15 year period. [PMID 12928689, PMID 10463402, PMID 17224761]

discussed in this [http://www.eyeondna.com/2007/08/11/only-one-gene-for-exfoliative-glaucoma/ blog post]

{{PMID|18385788|OA=1
}} [[rs1048661]] (G), [[rs3825942]] (C), and [[rs2165241]] (T) are highly associated with XFS and XFG in American and European populations. The GGT haplotype constitutes a major risk haplotype for exfoliation.

{{PMID|18385063}} Confirmed as risk for pseudoexfoliation (PEX) and pseudoexfoliation glaucoma (PEXG) in populations of German and Italian descent.

{{PMID|20431720|OA=1
}} Although not conducted with a large number of patients, in a study of black South Africans the [[rs3825942]](T) allele was the risk allele, in contrast to other populations.

{{ neighbor
| rsid = 1048661
| distance = 36
}}

{{GWAS Summary
|SNP=rs3825942
|PubMedID=17690259
|Condition=Exfoliation glaucoma
|Gene=LOXL1
|Risk Allele=C
|pValue=3.00E-021
|OR=20.1
|95CI=10.80-37.41
}}

{{PMID Auto
|PMID=19503743
|Title=Association of LOXL1 polymorphisms with pseudoexfoliation in the Chinese
|OA=1
}}

{{omim
|id=153456
|desc=LYSYL OXIDASE-LIKE 1; LOXL1
|rsnum=3825942
}}

{{PMID Auto
|PMID=19936304
|Title=Evaluation of LOXL1 polymorphisms in exfoliation syndrome in a Chinese population
|OA=1
}}

{{PharmGKB
|RSID=rs3825942
|Name_s=
|Gene_s=LOXL1
|Feature=
|Evidence=PubMed ID:17690259; Web Resource:http://www.genome.gov/gwastudies/
|Annotation=GWAS Results: Common sequence variants in the LOXL1 gene confer susceptibility to exfoliation glaucoma (Initial Sample Size: 75 cases, 14,474 controls; Replication Sample Size: 254 cases, 198 controls; Risk Allele: rs3825942-G).
|Drugs=
|Drug Classes=
|Diseases=Glaucoma
|Curation Level=Non-Curated
|PharmGKB Accession ID=PA162356688
}}

{{PharmGKB
|RSID=rs3825942
|Name_s=
|Gene_s=LOXL1
|Feature=
|Evidence=PubMed ID:17690259
|Annotation=In a case-control GWAS of Icelandic and Swedish patients, the G allele of rs3825942 was significantly associated with risk of Exfoliation Syndrome Glaucoma.
|Drugs=
|Drug Classes=
|Diseases=Exfoliation Syndrome
|Curation Level=Curated
|PharmGKB Accession ID=PA162355582
}}

{{PMID Auto
|PMID=21320968
|Title=An Investigation Into LOXL1 Variants in Black South African Individuals With Exfoliation Syndrome
}}

{{omim
|id=153456
|rsnum=3825942
|variant=0002
}}

{{PMID Auto
|PMID=21510775
|Title=Lack of association between LOXL1 gene polymorphisms and primary open angle glaucoma in the Saudi Arabian population
|OA=1
}}

{{PMID Auto
|PMID=21970694
|Title=Prevalence of high-risk alleles in the LOXL1 gene and its association with pseudoexfoliation syndrome and exfoliation glaucoma in a Latin American population
}}

{{PMID Auto
|PMID=22194657
|Title=Analysis of LOXL1 gene variants in Japanese patients with branch retinal vein occlusion
|OA=1
}}

{PMID Auto
|PMID=22065931
|Title=Decreased total antioxidants status in the plasma of patients with pseudoexfoliation glaucoma.
}}

{{PMID Auto
|PMID=22765198
|Title=TT polymorphism in rs2165241 and rs1048661 region in lysyl oxidase like-1 gene may have a role in stress urinary incontinence physiopathology
}}
<!-- see the talk page
An anonymous user points out at the risk allele is the reference. This is a 'error' in clinvar, but I believe it is the reason this one is flagged as 
|CLNSIG=255

Ideally this would be fixed upstream, and a change here might eventually be overwritten by a bot (hence the need for this comment). I could also introduce a new flag which explicitly flags the bad geno, and while defaulting to the current behavior.
-->
{{ClinVar
|rsid=3825942
|Reversed=0
|FwdREF=G
|FwdALT=A
|Risk=G
|REF=G
|ALT=A
|RSPOS=74219582
|CHROM=15
|GMAF=0.2248
|dbSNPBuildID=107
|SSR=0
|SAO=1
|VP=0x050168000000170517130100
|GENEINFO=LOXL1-AS1:100287616; LOXL1:4016
|GENE_NAME=LOXL1-AS1; LOXL1
|GENE_ID=100287616; 4016
|WGT=0
|VC=SNV
|CLNALLE=1
|CLNHGVS=NC_000015.9:g.74219582G>A
|CLNORIGIN=1
|CLNSIG=255
|Tags=PM;PMC;SLO;VLD;G5A;G5;HD;GNO;KGPhase1;KGPROD;OTHERKG;PH3;LSD;MTP;OM
|CAF=0.775; 0.225
|CLNACC=RCV000015435.1
|CLNDBN=Exfoliation syndrome, susceptibility to
|CLNSRC=OMIM Allelic Variant
|CLNSRCID=153456.0002
|COMMON=1
|Disease=Exfoliation syndrome
}}

{{PMID Auto
|PMID=17690546
|Title=Association between single nucleotide polymorphisms in the lysyl oxidase-like 1 gene and spontaneous cervical artery dissection.
}}

{{PMID Auto
|PMID=18201684
|Title=Lysyl oxidase-like 1 polymorphisms and exfoliation syndrome in the Japanese population.
}}

{{PMID Auto
|PMID=18223248
|Title=The LOXL1 gene variations are not associated with primary open-angle and primary angle-closure glaucomas.
}}

{{PMID Auto
|PMID=18224312
|Title=Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatment.
|OA=1
}}

{{PMID Auto
|PMID=18254956
|Title=DNA sequence variants in the LOXL1 gene are associated with pseudoexfoliation glaucoma in a U.S. clinic-based population with broad ethnic diversity.
|OA=1
}}

{{PMID Auto
|PMID=18287813
|Title=Genetic association of LOXL1 gene variants and exfoliation glaucoma in a Utah cohort.
}}

{{PMID Auto
|PMID=18334928
|Title=Analysis of LOXL1 polymorphisms in a United States population with pseudoexfoliation glaucoma.
|OA=1
}}

{{PMID Auto
|PMID=18334947
|Title=Association of non-synonymous single nucleotide polymorphisms in the LOXL1 gene with pseudoexfoliation syndrome in India.
|OA=1
}}

{{PMID Auto
|PMID=18421074
|Title=Lack of association between LOXL1 variants and primary open-angle glaucoma in three different populations.
|OA=1
}}

{{PMID Auto
|PMID=18450598
|Title=Association of LOXL1 gene polymorphisms with pseudoexfoliation in the Japanese.
}}

{{PMID Auto
|PMID=18483563
|Title=Lysyl oxidase-like protein 1 (LOXL1) gene polymorphisms and exfoliation glaucoma in a Central European population.
|OA=1
}}

{{PMID Auto
|PMID=18552979
|Title=LOXL1 genetic polymorphisms are associated with exfoliation glaucoma in the Japanese population.
|OA=1
}}

{{PMID Auto
|PMID=18618003
|Title=Exfoliation syndrome and exfoliation glaucoma-associated LOXL1 variations are not involved in pigment dispersion syndrome and pigmentary glaucoma.
|OA=1
}}

{{PMID Auto
|PMID=18636115
|Title=Lysyl oxidase-like 1 gene polymorphisms in Japanese patients with primary open angle glaucoma and exfoliation syndrome.
|OA=1
}}

{{PMID Auto
|PMID=18648524
|Title=Evaluation of LOXL1 polymorphisms in eyes with exfoliation glaucoma in Japanese.
|OA=1
}}

{{PMID Auto
|PMID=18958304
|Title=LOXL1 variants in elderly Japanese patients with exfoliation syndrome/glaucoma, primary open-angle glaucoma, normal tension glaucoma, and cataract.
|OA=1
}}

{{PMID Auto
|PMID=18974306
|Title=Genotype-correlated expression of lysyl oxidase-like 1 in ocular tissues of patients with pseudoexfoliation syndrome/glaucoma and normal patients.
|OA=1
}}

{{PMID Auto
|PMID=19098994
|Title=Evaluation of LOXL1 polymorphisms in primary open-angle glaucoma in southern and northern Chinese.
|OA=1
}}

{{PMID Auto
|PMID=19112534
|Title=Lack of association of polymorphisms in homocysteine metabolism genes with pseudoexfoliation syndrome and glaucoma.
|OA=1
}}

{{PMID Auto
|PMID=19279689
|Title=TNF-alpha -308 G>A and -238 G>A polymorphisms are not major risk factors in Caucasian patients with exfoliation glaucoma.
|OA=1
}}

{{PMID Auto
|PMID=19343041
|Title=Association of LOXL1 gene with Finnish exfoliation syndrome patients.
}}

{{PMID Auto
|PMID=21150032
|Title=Complex genetic mechanisms in glaucoma: an overview.
|OA=1
}}

{{PMID Auto
|PMID=21272281
|Title=Analysis of LOXL1 single nucleotide polymorphisms in Polish population with pseudoexfoliation syndrome.
}}

{{PMID Auto
|PMID=21364909
|Title=Eurasian and Sub-Saharan African mitochondrial DNA haplogroup influences pseudoexfoliation glaucoma development in Saudi patients.
|OA=1
}}

{{PMID Auto
|PMID=21559813
|Title=No association of LOXL1 gene polymorphisms with Alzheimer's disease.
}}

{{GET Evidence
|gene=LOXL1
|aa_change=Gly153Asp
|aa_change_short=G153D
|impact=pharmacogenetic
|qualified_impact=Insufficiently evaluated pharmacogenetic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs3825942
|overall_frequency_n=2331
|overall_frequency_d=10564
|overall_frequency=0.220655
|n_genomes=2
|n_genomes_annotated=0
|n_haplomes=1
|n_articles=1
|n_articles_annotated=1
|in_omim=Y
|in_gwas=Y
|in_pharmgkb=Y
|pph2_score=0.135
|nblosum100=4
|autoscore=2
|webscore=N
}}

{{PMID Auto
|PMID=22605916
|Title=Role of Lysyl oxidase-like 1 gene polymorphisms in Pakistani patients with pseudoexfoliative glaucoma
|OA=1
}}

{{PMID Auto
|PMID=23441117
|Title=Evaluation of lysyl oxidase-like 1 gene polymorphisms in pseudoexfoliation syndrome in a Korean population
|OA=1
}}

{{PMID Auto
|PMID=23869164
|Title=Association of lysyl oxidase-like 1 gene common sequence variants in Greek patients with pseudoexfoliation syndrome and pseudoexfoliation glaucoma
|OA=1
}}

{{PMID Auto
|PMID=24603551
|Title=Association between Polymorphisms in Lysyl Oxidase-Like 1 and Susceptibility to Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma
|OA=1
}}

{{PMID Auto
|PMID=24892565
|Title=Association of lysyl oxidase-like 1 gene polymorphisms in pseudoexfoliation syndrome and pseudoexfoliation glaucoma in a Spanish population
}}

{{PMID Auto
|PMID=24967207
|Title=Lack of association between lysyl oxidase-like 1 polymorphisms and primary open angle glaucoma: a meta-analysis
}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | HumanOmni1Quad}}
{{on chip | Illumina Human 1M}}