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rs3825942

From SNPedia

Orientationplus
Stabilizedminus
Geno Mag Summary
(C;C) 2.3 common but 10x higher glaucoma risk in most (but not all) populations
(C;T) 1.8 possibly lower glaucoma risk
(T;T) 2.5 10x to 27x lower risk of exfoliation glaucoma
ReferenceGRCh38 38.1/141
Chromosome15
Position73927241
GeneLOXL1, RNASEH2B
is asnp
is mentioned by
dbSNPrs3825942
ebirs3825942
HLIrs3825942
Exacrs3825942
Varsomers3825942
Maprs3825942
PheGenIrs3825942
hapmaprs3825942
1000 genomesrs3825942
hgdprs3825942
ensemblrs3825942
gopubmedrs3825942
geneviewrs3825942
scholarrs3825942
googlers3825942
pharmgkbrs3825942
gwascentralrs3825942
openSNPrs3825942
23andMers3825942
23andMe allrs3825942
SNP Nexus

SNPshotrs3825942
SNPdbers3825942
MSV3drs3825942
GWAS Ctlgrs3825942
GMAF0.225
Max Magnitude2.5
? (C;C) (C;T) (T;T) 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.

Neighborrs1048661
Distance36
GWAS
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

OMIM153456
DescLYSYL OXIDASE-LIKE 1; LOXL1
Variant
Relatedalso
[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

OMIM153456
Desc
Variant0002
Relatedalso
[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

ClinVar
Risk rs3825942(G;G)
Alt rs3825942(A;A)
Reference rs3825942(G;G)
Significance Other
Disease Exfoliation syndrome
Variation info
Gene LOXL1-AS1 LOXL1
CLNDBN Exfoliation syndrome, susceptibility to
Reversed 0
HGVS NC_000015.9:g.74219582G>A
CLNSRC OMIM Allelic Variant
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.


GET Evidence
LOXL1-G153D
aa_change Gly153Asp
aa_change_short G153D
impact pharmacogenetic
qualified_impact Insufficiently evaluated pharmacogenetic
overall_frequency 0.220655
summary



[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.