rs3825942
| Orientation | plus |
| Stabilized | plus |
| 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 |
| Reference | GRCh38.p7 38.3/150 |
| Chromosome | 15 |
| Position | 73927241 |
| Gene | LOXL1, LOXL1-AS1 |
| is a | snp |
| is | mentioned by |
| dbSNP | rs3825942 |
| dbSNP (classic) | rs3825942 |
| ClinGen | rs3825942 |
| ebi | rs3825942 |
| HLI | rs3825942 |
| Exac | rs3825942 |
| Gnomad | rs3825942 |
| Varsome | rs3825942 |
| LitVar | rs3825942 |
| Map | rs3825942 |
| PheGenI | rs3825942 |
| Biobank | rs3825942 |
| 1000 genomes | rs3825942 |
| hgdp | rs3825942 |
| ensembl | rs3825942 |
| geneview | rs3825942 |
| scholar | rs3825942 |
| rs3825942 | |
| pharmgkb | rs3825942 |
| gwascentral | rs3825942 |
| openSNP | rs3825942 |
| 23andMe | rs3825942 |
| SNPshot | rs3825942 |
| SNPdbe | rs3825942 |
| MSV3d | rs3825942 |
| GWAS Ctlg | rs3825942 |
| GMAF | 0.225 |
| Max Magnitude | 2.5 |
| ? | (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 20142848
]
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 18385788] 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] 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.
| 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 19503743] Association of LOXL1 polymorphisms with pseudoexfoliation in the Chinese
[PMID 19936304] 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 21510775] 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 22194657] 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 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 18224312] Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatment.
[PMID 18254956] 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 18334928] Analysis of LOXL1 polymorphisms in a United States population with pseudoexfoliation glaucoma.
[PMID 18334947] Association of non-synonymous single nucleotide polymorphisms in the LOXL1 gene with pseudoexfoliation syndrome in India.
[PMID 18421074] 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 18483563] Lysyl oxidase-like protein 1 (LOXL1) gene polymorphisms and exfoliation glaucoma in a Central European population.
[PMID 18552979] LOXL1 genetic polymorphisms are associated with exfoliation glaucoma in the Japanese population.
[PMID 18618003] Exfoliation syndrome and exfoliation glaucoma-associated LOXL1 variations are not involved in pigment dispersion syndrome and pigmentary glaucoma.
[PMID 18636115] Lysyl oxidase-like 1 gene polymorphisms in Japanese patients with primary open angle glaucoma and exfoliation syndrome.
[PMID 18648524] Evaluation of LOXL1 polymorphisms in eyes with exfoliation glaucoma in Japanese.
[PMID 18958304] LOXL1 variants in elderly Japanese patients with exfoliation syndrome/glaucoma, primary open-angle glaucoma, normal tension glaucoma, and cataract.
[PMID 18974306] Genotype-correlated expression of lysyl oxidase-like 1 in ocular tissues of patients with pseudoexfoliation syndrome/glaucoma and normal patients.
[PMID 19098994] Evaluation of LOXL1 polymorphisms in primary open-angle glaucoma in southern and northern Chinese.
[PMID 19112534] Lack of association of polymorphisms in homocysteine metabolism genes with pseudoexfoliation syndrome and glaucoma.
[PMID 19279689] 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 21150032] Complex genetic mechanisms in glaucoma: an overview.
[PMID 21272281] Analysis of LOXL1 single nucleotide polymorphisms in Polish population with pseudoexfoliation syndrome.
[PMID 21364909] 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 22605916] Role of Lysyl oxidase-like 1 gene polymorphisms in Pakistani patients with pseudoexfoliative glaucoma
[PMID 23441117] Evaluation of lysyl oxidase-like 1 gene polymorphisms in pseudoexfoliation syndrome in a Korean population
[PMID 23869164] Association of lysyl oxidase-like 1 gene common sequence variants in Greek patients with pseudoexfoliation syndrome and pseudoexfoliation glaucoma
[PMID 24603551] 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 24967207] 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 25709925] The association of LOXL1 polymorphisms with exfoliation syndrome/glaucoma: Meta-analysis
[PMID 26319397] 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 30405941] Three Single Nucleotide Polymorphisms of LOXL1' in a Turkish Population with Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma.
[PMID 31850260] 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.
