Association of LOXL1 gene with Finnish exfoliation syndrome patients

Lemmelä, Susanna; Forsman, Eva; Onkamo, Päivi; Nurmi, Hanna; Laivuori, Hannele; Kivelä, Tero; Puska, Päivi; Heger, Martin; Eriksson, Aldur W.; Forsius, Henrik; Järvelä, Irma

doi:10.1038/jhg.2009.28

Cited by 50 publications

(41 citation statements)

References 32 publications

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“…11 A unique genome-wide scan carried out with 75 PEX patients and 14 474 population-based control subjects allowed the detection of a strong association between two nonsynonymous single nucleotide polymorphisms (SNPs) in the lysyl oxidase-like 1 (LOXL1) gene and both PEX syndrome and PEXG in populations from Iceland and Sweden. 12 This association has been subsequently confirmed in many cohorts worldwide, [13][14][15][16][17][18][19][20][21][22] including our present group of PEX patients. 23 Aiming to reduce experimental costs, DNA-pooling analysis has gained interest as a potential alternative to individual genotyping.…”

Section: Introductionmentioning

confidence: 57%

Genome-wide association study with DNA pooling identifies variants at CNTNAP2 associated with pseudoexfoliation syndrome

et al. 2010

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Genetic and nongenetic factors contribute to development of pseudoexfoliation (PEX) syndrome, a complex, age-related, generalized matrix process frequently associated with glaucoma. To identify specific genetic variants underlying its etiology, we performed a genome-wide association study (GWAS) using a DNA-pooling approach. Therefore, equimolar amounts of DNA samples of 80 subjects with PEX syndrome, 80 with PEX glaucoma (PEXG) and 80 controls were combined into separate pools and hybridized to 500K SNP arrays (Affymetrix). Array probe intensity data were analyzed and visualized with expressly developed software tools GPFrontend and GPGraphics in combination with GenePool software. For replication, independent German cohorts of 610 unrelated patients with PEX/PEXG and 364 controls as well as Italian cohorts of 249 patients and 190 controls were used. Of 19, 17 SNPs showing significant allele frequency difference in DNA pools were confirmed by individual genotyping. Further single genotyping at CNTNAP2 locus revealed association between PEX/PEXG for two SNPs, which was confirmed in an independent German but not the Italian cohort. Both SNPs remained significant in the combined German cohorts even after Bonferroni correction (rs2107856: P c ¼0.0108, rs2141388: P c ¼0.0072). CNTNAP2 was found to be ubiquitously expressed in all human ocular tissues, particularly in retina, and localized to cell membranes of epithelial, endothelial, smooth muscle, glial and neuronal cells. Confirming efficiency of GWAS with DNA-pooling approach by detection of the known LOXL1 locus, our study data show evidence for association of CNTNAP2 with PEX syndrome and PEXG in German patients.

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Section: Introductionmentioning

confidence: 57%

Genome-wide association study with DNA pooling identifies variants at CNTNAP2 associated with pseudoexfoliation syndrome

et al. 2010

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“…Conversely, the association between the three SNPs and XFG has been strongest in studies performed on Scandinavian population (Lemmela et al 2009;Thorleifsson et al 2007) while linkage deviates in some populations. This suggests that even if other variations within LOXL1 are causing the phenotype, these might still be in strong linkage with the risk alleles the Swedish population used in the present.…”

Section: Discussionmentioning

confidence: 93%

“…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: 98%

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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“…Following the removal of duplicate articles and the screening process, 79 full-text articles were assessed for eligibility. Among these, 37 studies met the inclusion criteria and were included in the meta-analysis (Thorleifsson et al, 2007;Fingert et al, 2007;Fan et al, 2008;Hewitt et al, 2008;Fuse et al, 2008;Ozaki et al, 2008;Mossböck et al, 2008;Challa et al, 2008;Pasutto et al, 2008;Schlötzer-Schrehardt et al, 2008;Aragon-Martin et al, 2008;Yang et al, 2008;Hayashi et al, 2008;Tanito et al, 2008;Mabuchi et al, 2008;Mori et al, 2008;Ramprasad et al, 2008;Lee et al, 2009;Chen et al, 2009;Lemmelä et al, 2009;Wolf et al, 2010;AbuAmero et al, 2010;Williams et al, 2010;Mayinu & Chen et al, 2011;Malukiewicz et al, 2011;Sagong et al, 2011;Abu-Amero et al, 2011;Rautenbach et al, 2011;Jaimes et al, 2012;Micheal et al, 2012;Chiras et al, 2013;Metaxaki et al, 2013;Kasım et al, 2013;Park et al, 2013;Anastasopoulos et al, 2014;Dubey et al, 2014;de Juan-Marcos et al, 2014). In two of these studies (Thorleifsson et al, 2007;…”

Section: Resultsmentioning

confidence: 99%

Ethnicity‐Based Differences in the Association of LOXL1 Polymorphisms with Pseudoexfoliation/Pseudoexfoliative Glaucoma: A Meta‐Analysis

Founti

Haidich

Chatzikyriakidou

et al. 2015

Annals of Human Genetics

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Pseudoexfoliation (PEX) is an age-related disorder of the extracellular matrix; it is strongly associated with glaucoma, the leading cause of irreversible blindness worldwide. We conducted an ethnic-based meta-analysis of the association of LOXL1 polymorphisms with PEX/pseudoexfoliative glaucoma (PEXG). Association studies were retrieved systematically from PubMed, EMBASE, and Web of Knowledge. Allelic and genotype frequencies of rs3825942, rs1048661, and rs2165241 were compared between PEX/PEXG and controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using a random effects model. Overall, 39 independent cohorts were included. Rs3825942 (G) was an at risk allele for PEX/PEXG in Caucasians, Japanese, Koreans, Chinese, South Asians, and Middle Easterners, but protective in Black South Africans (OR = 0.10, 95%CI:0.06-0.16). Rs1048661 (G) was an at risk allele for PEX/PEXG in Caucasians, South Asians, Middle Easterners and Black South Africans, but was protective in Japanese (OR = 0.03, 95%CI:0.02-0.06) and Koreans (OR = 0.10, 95%CI:0.05-0.22). These associations we-re confirmed for the genotypic recessive models. Rs2165241 (C) was a protective allele for PEX/PEXG in Caucasians, but was an at risk allele in Japanese (OR = 7.49, 95%CI:3.22-17.41) and Koreans (OR = 6.63, 95%CI:2.60-16.90). This was confirmed for the genotypic dominant model. Other genetic and/or environmental factors may modify the effect of LOXL1 polymorphisms in certain ethnic groups.

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Association of LOXL1 gene with Finnish exfoliation syndrome patients

Cited by 50 publications

References 32 publications

Genome-wide association study with DNA pooling identifies variants at CNTNAP2 associated with pseudoexfoliation syndrome

Genome-wide association study with DNA pooling identifies variants at CNTNAP2 associated with pseudoexfoliation syndrome

No Association of LOXL1 Gene Polymorphisms with Alzheimer’s Disease

Ethnicity‐Based Differences in the Association of LOXL1 Polymorphisms with Pseudoexfoliation/Pseudoexfoliative Glaucoma: A Meta‐Analysis

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