Association of<i>LOXL1</i>Gene Polymorphisms with Pseudoexfoliation in the Japanese

Ozaki, Mineo; Lee, Kelvin Y. C.; Vithana, Eranga N.; Yong, Victor H. K.; Thalamuthu, Anbupalam; Mizoguchi, Takanori; Venkatraman, Anandalakshmi; Aung, Tin

doi:10.1167/iovs.08-1805

Cited by 77 publications

(61 citation statements)

References 29 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%

“…Hence, only the risk allele G of rs3825942 is associated with XFS in both the populations. [31][32][33] Consistently, the high-risk haplotype in the Japanese is TG, composed of coding SNPs, and TGC, composed of all three SNPs, compared with GG and GGT in Caucasians. [31][32][33][34][35] In the Finnish case-control material, the haplotype GGT increased the risk of XFS and XFG more than threefold, whereas in the Japanese population GGT haplotype was very rare and TGC increased the risk of XFS nearly threefold.…”

Section: Discussionmentioning

confidence: 99%

“…[31][32][33] Consistently, the high-risk haplotype in the Japanese is TG, composed of coding SNPs, and TGC, composed of all three SNPs, compared with GG and GGT in Caucasians. [31][32][33][34][35] In the Finnish case-control material, the haplotype GGT increased the risk of XFS and XFG more than threefold, whereas in the Japanese population GGT haplotype was very rare and TGC increased the risk of XFS nearly threefold. 32 The fact that allele G of rs3825942 is the only exfoliation-associated allele in all the populations [31][32][33] suggests that it is the most likely source of association in the LOXL1 gene.…”

Section: Discussionmentioning

confidence: 99%

“…[31][32][33][34][35] In the Finnish case-control material, the haplotype GGT increased the risk of XFS and XFG more than threefold, whereas in the Japanese population GGT haplotype was very rare and TGC increased the risk of XFS nearly threefold. 32 The fact that allele G of rs3825942 is the only exfoliation-associated allele in all the populations [31][32][33] suggests that it is the most likely source of association in the LOXL1 gene. Moreover, in a study of Caucasian and African-American patients in the United States, a strong association was found for SNPs rs3825942 and rs2165241, but not for rs1048661, and the linkage disequilibrium (LD) between two coding SNPs was very weak (D¢¼0.09, r 2 ¼0), which suggests that the effect of rs3825942 is independent of rs1048661.…”

Section: Discussionmentioning

confidence: 99%

“…26 The difference in the alleles flanking the causal G allele of rs3825942 might be explained by the independent origin of the rs3825942 in different genetic backgrounds or by different recombinations around this possibly ancient mutation in the Caucasian and Japanese populations. On the other hand, a strong LD between rs1048661 and rs3825942 was shown in the Nordic (D¢¼1) and Japanese populations (D¢¼1), 11,32,33 and conditional analysis in the Japanese study showed that rs3825942 was highly correlated with rs1048661, which, on the contrary, indicates that rs3825942 is not independent of rs1048661. 32 Hence, the possibility that causative variant is in a state of LD with LOXL1 SNPs, and yet to be discovered, cannot be excluded.…”

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: Discussionmentioning

confidence: 99%

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 ofLOXL1Gene Polymorphisms with Pseudoexfoliation in the Japanese

Abstract: Polymorphisms in the LOXL1 gene confer risk to XFS/XFG in the Japanese, but there are different risk-associated alleles and haplotypes in the Japanese.

Cited by 77 publications

References 29 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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