Genetic association of LOXL1 gene variants and exfoliation glaucoma in a Utah cohort

Yang, Xian; Zabriskie, Norman A.; Hau, Vincent; Chen, Haoyu; Tong, Zongzhong; Gibbs, Daniel; Farhi, Parisa; Katz, Bradley J.; Luo, Ling; Pearson, Erik; Goldsmith, J.; Ma, Xiang; Kaminoh, Yukki; Chen, Yuhong; Yu, Baifeng; Zeng, Junjie; Zhang, Kang; Yang, Zhenglin

doi:10.4161/cc.7.4.5388

Cited by 43 publications

(23 citation statements)

References 23 publications

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“…This is in agreement with the earlier studies in other Caucasian populations (Scandinavians, 11 and other European [23][24][25][26] and American populations 25,[27][28][29], in the Australian population 30 and also in AfricanAmericans 26 and in the Asian populations from Japan [31][32][33][34][35] and India. 36 The strongest allelic effect in the Finnish case-control material was found for allele G of exonic SNP rs3825942, which confers the greatest risk in all populations studied so far.…”

Section: Discussionsupporting

confidence: 92%

Association of LOXL1 gene with Finnish exfoliation syndrome patients

et al. 2009

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In this study, three single-nucleotide polymorphisms (SNPs) on the lysyl oxidase-like 1 (LOXL1) gene associated with exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) were investigated in the Finnish population. A case-control study of 59 sporadic patients with XFS, 82 with XFG, 71 with primary open-angle glaucoma (POAG) and 26 individuals without these disorders from the southern Finnish population, and a family study of an extended family with 28 patients with XFS or XFG and 92 unaffected relatives from Kö kar islands, Southwestern Finnish archipelago, were conducted. Anonymous blood donors (n¼404) were studied as population-based controls. Three SNPs, rs1048661 (R141L), rs3825942 (G153D) and rs2165241, of the LOXL1 gene were genotyped by PCR sequencing. Association and linkage analyses were carried out. In both case-control and family materials, significant association for allele G of rs1048661 (P¼2.65Â10 À5 ; P¼0.0007), allele G of rs3825942 (P¼2.24Â10 À8 ; P¼0.49) and allele T of rs2165241 (P¼2.62Â10 À13 ; Po0.0001) was found in XFS/XFG. However, linkage was not observed for LOXL1 risk alleles. The corresponding three-locus haplotype GGT increased the risk of XFS/ XFG nearly 15-fold relative to low-risk haplotype GAC (odds ratio (OR): 14.9, P¼1.6Â10 À16 ). In conclusion, the earlier reported polymorphisms of the LOXL1 gene showed significant association also in the Finnish population.

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Section: Discussionsupporting

confidence: 92%

Association of LOXL1 gene with Finnish exfoliation syndrome patients

et al. 2009

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“…Although the risk haplotype differs with different populations, a strong association between the SNPs on LOXL1 and exfoliation glaucoma has been replicated in many studies (18)(19)(20)(21)(22)(23)(24)(25)(26), including ours of Japanese subjects (27), even when the sample size was relatively small. However, in our GWAS, in which the power was sufficient to detect SNPs with a high genotype risk ratio (Fig.…”

Section: ϫ7mentioning

confidence: 76%

Three susceptible loci associated with primary open-angle glaucoma identified by genome-wide association study in a Japanese population

Nakano¹,

Ikeda

Taniguchi

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

100

109

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Primary open-angle glaucoma (POAG) is the major type of glaucoma. To discover genetic markers associated with POAG, we examined a total of 1,575 Japanese subjects in a genome-wide association study (stage 1) and a subsequent study (stage 2). Both studies were carried out at a single institution. In the stage 1 association study, we compared SNPs between 418 POAG patients and 300 control subjects. First, low-quality data were eliminated by a stringent filter, and 331,838 autosomal SNPs were selected for analysis. Poorly clustered SNPs were eliminated by a visual assessment, leaving 255 that showed a significant deviation (P < 0.001) in the allele frequency comparison. In the stage 2 analysis, we tested these 255 SNPs for association in DNA samples from a separate group of 409 POAG and 448 control subjects. High-quality genotype data were selected and used to calculate the combined P values of stages 1 and 2 by the Mantel-Haenszel test. These analyses yielded 6 SNPs with P < 0.0001. All 6 SNPs showed a significant association (P < 0.05) in stage 2, demonstrating a confirmed association with POAG. Although we could not link the SNPs to the annotated gene(s), it turned out that we have identified 3 genetic loci probably associated with POAG. These findings would provide the foundation for future studies to build on, such as for the metaanalysis, to reveal the molecular mechanism of the POAG pathogenesis.diagnosis ͉ SNP ͉ GWAS ͉ meta-analysis ͉ glaucoma genetics

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“…In the present study, analyses of patients with AD and healthy controls were performed for genotypes of three XFS/XFG-associated SNPs in LOXL1 (Aragon- Martin et al 2008;Challa et al 2008;Chen et al 2009Chen et al , 2010Fan et al 2008;Fuse et al 2008;Hayashi et al 2008;Lee et al 2009;Lemmela et al 2009;Mori et al 2008;Mossbock et al 2008;Ozaki et al 2008;Pasutto et al 2008;Ramprasad et al 2008;Tanito et al 2008;Thorleifsson et al 2007;Williams et al 2010;Yang et al 2008). Allele and genotype frequencies were examined in relation to clinical diagnosis and CSF biomarkers for AD.…”

Section: Discussionmentioning

confidence: 99%

No Association of LOXL1 Gene Polymorphisms with Alzheimer’s Disease

et al. 2011

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Aggregation of amyloid-beta is one of the major characteristics in brains of patients with Alzheimer's disease (AD). Although several mechanisms behind the formation of such aggregates have been suggested the regulatory factors are still unknown. The present study aimed at investigating the association of lysyl oxidase-like 1 (LOXL1) polymorphisms with AD diagnosis and cerebrospinal fluid biomarkers (CSF) for the disease. Proteins of the lysyl oxidase (LOX) family are involved in cross-linking extracellular matrix proteins to insoluble fibers and have been associated with neurodegenerative diseases including AD. Genetic polymorphisms in LOXL1 (rs1048661, rs3825942, and rs2165241) have been linked to exfoliation syndrome and exfoliation glaucoma, conditions that have shown association with AD. The polymorphisms were genotyped by Taqman allelic discrimination in a study sample including AD patients (n = 318) and controls (n = 575). In a subgroup of the population, the polymorphisms were analyzed in relation to APOE ε4 genotype and to CSF (T-tau, P-tau, and Aβ(1-42)). No evidence for associations of these polymorphisms with risk for AD or any of the studied CSF biomarkers measured was found. These results do not support LOXL1 as being a major risk gene for AD.

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Genetic association of LOXL1 gene variants and exfoliation glaucoma in a Utah cohort

Cited by 43 publications

References 23 publications

Association of LOXL1 gene with Finnish exfoliation syndrome patients

Association of LOXL1 gene with Finnish exfoliation syndrome patients

Three susceptible loci associated with primary open-angle glaucoma identified by genome-wide association study in a Japanese population

No Association of LOXL1 Gene Polymorphisms with Alzheimer’s Disease

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