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From SNPedia

Geno Mag Summary
(A;A) 2.5 10x to 27x lower risk of exfoliation glaucoma
(A;G) 1.8 possibly lower glaucoma risk
(G;G) 2.3 common but 10x higher glaucoma risk in most (but not all) populations
ReferenceGRCh38.p7 38.3/150
is asnp
is mentioned by
dbSNP (classic)rs3825942
1000 genomesrs3825942
GWAS Ctlgrs3825942
Max Magnitude2.5
? (A;A) (A;G) (G;G) 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 20142848OA-icon.png]

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 blog post

[PMID 18385788OA-icon.png] 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 20431720OA-icon.png] 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.

SNP rs3825942
PubMedID [PMID 17690259]
Condition Exfoliation glaucoma
Gene LOXL1
Risk Allele C
pValue 3.00E-021
OR 20.1
95% CI 10.80-37.41

[PMID 19503743OA-icon.png] Association of LOXL1 polymorphisms with pseudoexfoliation in the Chinese


[PMID 19936304OA-icon.png] Evaluation of LOXL1 polymorphisms in exfoliation syndrome in a Chinese population

[PMID 21320968] An Investigation Into LOXL1 Variants in Black South African Individuals With Exfoliation Syndrome


[PMID 21510775OA-icon.png] Lack of association between LOXL1 gene polymorphisms and primary open angle glaucoma in the Saudi Arabian population

[PMID 21970694] Prevalence of high-risk alleles in the LOXL1 gene and its association with pseudoexfoliation syndrome and exfoliation glaucoma in a Latin American population

[PMID 22194657OA-icon.png] Analysis of LOXL1 gene variants in Japanese patients with branch retinal vein occlusion

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

[PMID 22765198] TT polymorphism in rs2165241 and rs1048661 region in lysyl oxidase like-1 gene may have a role in stress urinary incontinence physiopathology

Risk Rs3825942(G;G)
Alt Rs3825942(A;A)
Reference Rs3825942(G;G)
Significance Other
Disease Exfoliation syndrome
Variation info
CLNDBN Exfoliation syndrome, susceptibility to
Reversed 0
HGVS NC_000015.9:g.74219582G>A
CLNSRC OMIM Allelic Variant UniProtKB (protein)
CLNACC RCV000015435.2,

[PMID 17690546] Association between single nucleotide polymorphisms in the lysyl oxidase-like 1 gene and spontaneous cervical artery dissection.

[PMID 18201684] Lysyl oxidase-like 1 polymorphisms and exfoliation syndrome in the Japanese population.

[PMID 18223248] The LOXL1 gene variations are not associated with primary open-angle and primary angle-closure glaucomas.

[PMID 18224312OA-icon.png] Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatment.

[PMID 18254956OA-icon.png] DNA sequence variants in the LOXL1 gene are associated with pseudoexfoliation glaucoma in a U.S. clinic-based population with broad ethnic diversity.

[PMID 18287813] Genetic association of LOXL1 gene variants and exfoliation glaucoma in a Utah cohort.

[PMID 18334928OA-icon.png] Analysis of LOXL1 polymorphisms in a United States population with pseudoexfoliation glaucoma.

[PMID 18334947OA-icon.png] Association of non-synonymous single nucleotide polymorphisms in the LOXL1 gene with pseudoexfoliation syndrome in India.

[PMID 18421074OA-icon.png] Lack of association between LOXL1 variants and primary open-angle glaucoma in three different populations.

[PMID 18450598] Association of LOXL1 gene polymorphisms with pseudoexfoliation in the Japanese.

[PMID 18483563OA-icon.png] Lysyl oxidase-like protein 1 (LOXL1) gene polymorphisms and exfoliation glaucoma in a Central European population.

[PMID 18552979OA-icon.png] LOXL1 genetic polymorphisms are associated with exfoliation glaucoma in the Japanese population.

[PMID 18618003OA-icon.png] Exfoliation syndrome and exfoliation glaucoma-associated LOXL1 variations are not involved in pigment dispersion syndrome and pigmentary glaucoma.

[PMID 18636115OA-icon.png] Lysyl oxidase-like 1 gene polymorphisms in Japanese patients with primary open angle glaucoma and exfoliation syndrome.

[PMID 18648524OA-icon.png] Evaluation of LOXL1 polymorphisms in eyes with exfoliation glaucoma in Japanese.

[PMID 18958304OA-icon.png] LOXL1 variants in elderly Japanese patients with exfoliation syndrome/glaucoma, primary open-angle glaucoma, normal tension glaucoma, and cataract.

[PMID 18974306OA-icon.png] Genotype-correlated expression of lysyl oxidase-like 1 in ocular tissues of patients with pseudoexfoliation syndrome/glaucoma and normal patients.

[PMID 19098994OA-icon.png] Evaluation of LOXL1 polymorphisms in primary open-angle glaucoma in southern and northern Chinese.

[PMID 19112534OA-icon.png] Lack of association of polymorphisms in homocysteine metabolism genes with pseudoexfoliation syndrome and glaucoma.

[PMID 19279689OA-icon.png] TNF-alpha -308 G>A and -238 G>A polymorphisms are not major risk factors in Caucasian patients with exfoliation glaucoma.

[PMID 19343041] Association of LOXL1 gene with Finnish exfoliation syndrome patients.

[PMID 21150032OA-icon.png] Complex genetic mechanisms in glaucoma: an overview.

[PMID 21272281] Analysis of LOXL1 single nucleotide polymorphisms in Polish population with pseudoexfoliation syndrome.

[PMID 21364909OA-icon.png] Eurasian and Sub-Saharan African mitochondrial DNA haplogroup influences pseudoexfoliation glaucoma development in Saudi patients.

[PMID 21559813] No association of LOXL1 gene polymorphisms with Alzheimer's disease.

[PMID 22605916OA-icon.png] Role of Lysyl oxidase-like 1 gene polymorphisms in Pakistani patients with pseudoexfoliative glaucoma

[PMID 23441117OA-icon.png] Evaluation of lysyl oxidase-like 1 gene polymorphisms in pseudoexfoliation syndrome in a Korean population

[PMID 23869164OA-icon.png] Association of lysyl oxidase-like 1 gene common sequence variants in Greek patients with pseudoexfoliation syndrome and pseudoexfoliation glaucoma

[PMID 24603551OA-icon.png] Association between Polymorphisms in Lysyl Oxidase-Like 1 and Susceptibility to Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma

[PMID 24892565] Association of lysyl oxidase-like 1 gene polymorphisms in pseudoexfoliation syndrome and pseudoexfoliation glaucoma in a Spanish population

[PMID 24967207OA-icon.png] Lack of association between lysyl oxidase-like 1 polymorphisms and primary open angle glaucoma: a meta-analysis

[PMID 25304275] LOXL1 Gene Polymorphism With Exfoliation Syndrome/Exfoliation Glaucoma: A Meta-Analysis

[PMID 25709925OA-icon.png] The association of LOXL1 polymorphisms with exfoliation syndrome/glaucoma: Meta-analysis

[PMID 26319397OA-icon.png] LOXL1 gene variants and their association with pseudoexfoliation glaucoma (XFG) in Spanish patients

[PMID 27116380] Correlation of Aqueous Humor Lysyl Oxidase Activity with TGF-ß Levels and LOXL1 Genotype in Pseudoexfoliation.

[PMID 30405941OA-icon.png] Three Single Nucleotide Polymorphisms of LOXL1' in a Turkish Population with Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma.

[PMID 31850260OA-icon.png] Association of LOXL1 Gene Polymorphisms with Exfoliation Glaucoma Patients.

[PMID 32253563] Associations of polymorphisms in LOXL1 and copper chaperone genes with pseudoexfoliation-syndrome-related cataract in a Chinese Uygur population.