{{Rsnum
|rsid=1048661
|Gene=LOXL1
|Chromosome=15
|position=73927205
|Orientation=plus
|ReferenceAllele=G
|MissenseAllele=T
|GMAF=0.32
|Gene_s=LOXL1,RNASEH2B
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(G;G)
|geno2=(G;T)
|geno3=(T;T)
}}[[rs1048661]], also known as R141L, a SNP causing an amino acid change in the lysyl oxidase 1 [[LOXL1]] gene, has been linked to exfoliation [[glaucoma]]. This form of glaucoma causes up to 10% of the cases of blindness in many countries, including the US. [Science DOI: 10.1126/science.1146554] From the abstract of this study: "Approximately 25% of the general population is homozygous for the highest risk haplotype 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 [[rs1048661]](G), and it confers a estimated relative risk (by itself) of 3.04. The odds ratio is 2.46 (CI 1.91-3.16). [Note that the (G) allele is actually quite common in most European populations.]

However, a meta-analysis published in 2010 concluded that it's likely that SNPs [[rs1048661]] and [[rs2165241]] are not directly implicated in the pathogenesis of [[glaucoma]]; only the nearby [[rs3825942]] seemed to be the disease-associated SNP.{{PMID|20142848|OA=1
}}

In the original publications, the haplotypes identified as being of highest risk consisted of the combination of two SNPs together, [[rs1048661]](G) and [[rs3825942]](C), oriented with respect to the dbSNP entry. In the two populations studied combined (from Iceland and Sweden), the (G;C) haplotype has an odds ratio of 27.05, and the (T;C) haplotype has an OR of 8.90, relative to the (G;T) haplotype. The (T;T) haplotype is presumed to be at even lower risk than the (G;T) haplotype, but due at least in part to the high frequency of the [[rs1048661]](G) allele, no individuals in this study carried it. In the populations studied, ~25% of all individuals in the population carry two copies of the (G;C), highest risk haplotype.

If the risk of carrying two such haplotypes is multiplicative (which isn't known actually), the authors estimate that individuals carrying two copies of the (G;C) high risk haplotype would have 700 times the risk of developing this type of glaucoma compared to individuals carrying two copies of the (G;T) haplotype. Overall, (G;C) individuals are at ~2.5 fold higher risk than the average person in the populations studied.

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

{{ neighbor
| rsid = 3825942
| distance = 36
}}

{{PMID|18385788|OA=1
}} [[rs1048661]] (G), [[rs3825942]] (G), 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 Auto
|PMID=19503743
|Title=Association of LOXL1 polymorphisms with pseudoexfoliation in the Chinese
|OA=1
}}

{{omim
|desc=LYSYL OXIDASE-LIKE 1; LOXL1
|id=153456
|rsnum=1048661
|variant=0001
}}
{{PMID Auto
|PMID=19936304
|Title=Evaluation of LOXL1 polymorphisms in exfoliation syndrome in a Chinese population
|OA=1
}}

{{PharmGKB
|RSID=rs1048661
|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 rs1048661 was significantly associated with risk of Exfoliation Syndrome Glaucoma.
|Drugs=
|Drug Classes=
|Diseases=Exfoliation Syndrome
|Curation Level=Curated
|PharmGKB Accession ID=PA162355581
}}

{{PMID Auto
|PMID=20431720
|Title=Major LOXL1 risk allele is reversed in exfoliation glaucoma in a black South African population
|OA=1
}}

{{PMID Auto
|PMID=21320968
|Title=An Investigation Into LOXL1 Variants in Black South African Individuals With Exfoliation Syndrome
}}
{{omim
|id=153456
|rsnum=1048661
|variant=0001
}}

{{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.
|OA=1
}}

{{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
}}

{{ClinVar
|rsid=1048661
|Reversed=0
|FwdREF=G
|FwdALT=T
|REF=G
|ALT=T
|RSPOS=74219546
|CHROM=15
|GMAF=0.3191
|dbSNPBuildID=86
|SSR=0
|SAO=1
|VP=0x050168000000150516110100
|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.74219546G>T
|CLNORIGIN=1
|CLNSIG=255
|Tags=PM;PMC;SLO;VLD;G5;HD;GNO;KGPhase1;KGPROD;OTHERKG;LSD;OM
|CAF=0.68; 0.32
|CLNACC=RCV000015434.1
|CLNDBN=Exfoliation syndrome, susceptibility to
|CLNSRC=OMIM Allelic Variant
|CLNSRCID=153456.0001
|COMMON=1
|Disease=Exfoliation syndrome
}}

{{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=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=19373106
|Title=Lysyl oxidase-like 1 gene polymorphisms in German patients with normal tension glaucoma, pigmentary glaucoma and exfoliation glaucoma.
}}

{{PMID Auto
|PMID=19779542
|Title=A genome-wide association analysis identified a novel susceptible locus for pathological myopia at 11q24.1.
|OA=1
}}

{{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=Arg141Leu
|aa_change_short=R141L
|impact=benign
|qualified_impact=Low clinical importance, Uncertain benign
|inheritance=other
|quality_scores=Array
|dbsnp_id=rs1048661
|overall_frequency_n=2646
|overall_frequency_d=10340
|overall_frequency=0.255899
|n_genomes=3
|n_genomes_annotated=0
|n_haplomes=1
|n_articles=3
|n_articles_annotated=3
|qualityscore_in_silico=!
|qualitycomment_in_silico=Y
|qualityscore_in_vitro=0
|qualitycomment_in_vitro=Y
|qualityscore_case_control=0
|qualitycomment_case_control=Y
|in_omim=Y
|in_pharmgkb=Y
|pph2_score=0.998
|nblosum100=6
|autoscore=3
|webscore=N
|variant_evidence=0
|clinical_importance=0
|summary_short=Associated with exfoliative glaucoma & syndrome (XFG & XFS) in various populations, but with contradicting results (protective in Caucasians, pathogenic in Japanese). Based on this it seems the variation itself -- although it affects protein structure -- is not itself causing disease. Instead it is likely associated with other nearby causal variants. As such, it is evaluated as benign by GET-Evidence (which focuses on reporting causal variants). See detailed variant report for disease risk associations.
}}

{{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}}