Association of<i>LOXL1</i>Common Sequence Variants in German and Italian Patients with Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma

Pasutto, Francesca; Krumbiegel, Mandy; Mardin, Christian Y.; Paoli, Daniela; Laemmer, Robert; Weber, Bernhard H. F.; Kruse, Friedrich E.; Schlötzer‐Schrehardt, Ursula; Reis, André

doi:10.1167/iovs.07-1449

Cited by 95 publications

(52 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%

“…The same proportion of GG homozygotes was reported earlier in German and Italian exfoliation patients. 24 Together GG and TG haplotypes accounted for 97% of the exfoliation cases, being in agreement with the corresponding results in Scandinavian (99%) and other European populations (96%). 11,25 On the other hand, the high-risk haplotype GG is also very common in the general population, with an average frequency of 72% in Finland, 50% in Iceland and Sweden and 50% in unaffected individuals in other European populations.…”

Section: Discussionsupporting

confidence: 91%

“…The two-locus haplotype GG of coding SNPs rs1048661-rs3825942 was highly overrepresented, whereas TG and GA haplotypes were underrepresented in XFS and XFG cases compared with the population-based controls, which is convergent with earlier studies of Caucasian populations. 11,[23][24][25] The high-risk haplotype GG was present in 95% of the Finnish exfoliation cases and two copies of GG haplotype (GG homozygosity) were identified in 66% of patients. The same proportion of GG homozygotes was reported earlier in German and Italian exfoliation patients.…”

Section: Discussionmentioning

confidence: 99%

“…11,25 The homozygous GG haplotype was found in 29% of individuals in the general Finnish population, 25% in Iceland and Sweden populations, and 27% in healthy controls from German and Italy. 11,24 The high-risk haplotype frequencies in the Finnish general population can partly be explained by the high prevalence of exfoliation in Scandinavia (22% of the population 470 years old in Finland), and by the fact that controls were not age matched and some of them might develop XFS and XFG in their later years.…”

Section: Discussionmentioning

confidence: 99%

“…11,[23][24][25] The GGT haplotype was present in 93% of the exfoliation cases and 69% of the population-based controls. The GGT increased the risk for XFS and XFG almost 15-fold and the TGC increased the risk nearly fivefold relative to the low-risk GAC haplotype.…”

Section: Discussionmentioning

confidence: 99%

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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%

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Association of LOXL1 gene with Finnish exfoliation syndrome patients

et al. 2009

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An Investigation Into LOXL1 Variants in Black South African Individuals With Exfoliation Syndrome

Rautenbach

Bardien²,

Harvey³

et al. 2011

Arch Ophthalmol

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Objective: To investigate the association between 2 lysyl oxidase-like 1 (LOXL1) polymorphisms, rs1048661 (R141L) and rs3825942 (G153D), and exfoliation syndrome (XFS) in black South African individuals. Methods: A total of 43 black patients with XFS and 47 ethnically matched controls were recruited for genetic analysis. Samples were analyzed for presence of the LOXL1-R141L and G153D variants using restriction fragment length polymorphism analysis. A case-control association study was performed. Results: The R141L and G153D single-nucleotide polymorphisms (SNPs) were both significantly associated with XFS (P = .00582 and P Ͻ .00001, respectively). Consistent with findings in white populations but not in Asian cohorts, the GG genotype of the R141L SNP was present in significantly more XFS cases than controls (P=.00582). However, in this black South African study population, the AA genotype of G153D was present in an overwhelming majority of cases with XFS (P Ͻ .00001; odds ratio, 17.10; 95% confidence interval, 4.91-59.56), contrary to all previous articles in which the GG genotype was strongly associated with the disease phenotype. Conclusion: The LOXL1 SNPs R141L and G153D are significantly associated with XFS in this black South African population. The AA genotype of G153D confers XFS risk in this population, as opposed to the GG genotype described in all other populations, suggesting that unidentified genetic or environmental factors independent of these LOXL1 SNPs may influence phenotypic expression of the syndrome. Clinical Relevance: Elucidation of the role of genetic factors, including the LOXL1 gene, in XFS will facilitate identification of individuals predisposed to developing this condition.

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Lysyl Oxidase–Like 1 Gene in the Reversal of Promoter Risk Allele in Pseudoexfoliation Syndrome

et al. 2014

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IMPORTANCE This study was necessary to establish the association between common genetic variants in the lysyl oxidase-like 1 (LOXL1) gene with pseudoexfoliation (PEX) syndrome and emphasize the reversal of promoter risk allele in a South Indian population.OBJECTIVE To investigate the potential association of genetic variants across the LOXL1 gene in South Indian patients with PEX syndrome and glaucoma. DESIGN, SETTING, AND PARTICIPANTSA case-control study of individuals from Madurai, India, with PEX syndrome and glaucoma as well as healthy people serving as controls. Three hundred unrelated people with PEX syndrome and 225 age-and ethnically matched controls were recruited for genetic analysis. MAIN OUTCOMES AND MEASURESFour single-nucleotide polymorphisms in LOXL1 (rs16958477, rs1048661, rs3825942, and rs2165241) were genotyped by direct sequencing in all participants. Regulatory regions and 7 coding exons of LOXL1 were directly sequenced in 50 patients and 50 controls. A case-control association analysis was performed using the Golden Helix SVS suite.RESULTS An association between 4 LOXL1 single-nucleotide polymorphisms with PEX syndrome and glaucoma was observed (rs16958477,

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Association ofLOXL1Common Sequence Variants in German and Italian Patients with Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma

Abstract: Genetic variants in LOXL1 confer risk to PEX in German and Italian populations, independent of the presence of secondary glaucoma, confirming findings in patients from Northern Europe.

Cited by 95 publications

References 23 publications

Association of LOXL1 gene with Finnish exfoliation syndrome patients

Association of LOXL1 gene with Finnish exfoliation syndrome patients

An Investigation Into LOXL1 Variants in Black South African Individuals With Exfoliation Syndrome

Lysyl Oxidase–Like 1 Gene in the Reversal of Promoter Risk Allele in Pseudoexfoliation Syndrome

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