LOXL1 Gene Polymorphism With Exfoliation Syndrome/Exfoliation Glaucoma

Wang, Lin; Yu, Yongbin; Fu, Songbin; Zhao, Wencheng; Liu, Ping

doi:10.1097/ijg.0000000000000128

Cited by 36 publications

(35 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Interestingly, there is evidence of nominal association for both CLU SNPs (rs3087554 in the Japanese dataset and rs2279590 in the Indian datasets) despite the differences in direction of effect, which may be caused by ‘flipping’ of the risk allele due to population specific effects (Lin et al, 2007). This is a recognized phenomenon in disease association studies including the association of LOXL1 with XFS where commonly associated SNPs are ‘flipped’ in some Asian populations and in the South Africans (Wang et al, 2014; Dubey et al, 2014; Williams et al, 2010). Alternatively, the observed associations between CLU SNPs in the Indian and Japanese populations may be spurious findings.…”

Section: Discussionmentioning

confidence: 99%

“…A genome-wide association study (GWAS) using unrelated patients and controls from Iceland and Sweden revealed significant association between common lysyl oxidase-like 1 ( LOXL1 ) variants and XFS (Thorleifsson et al, 2007). This association was subsequently replicated in populations worldwide (Wang et al, 2014), including in United States clinic-based samples (Fingert et al, 2007; Aragon-Martin et al, 2008; Challa et al, 2008; Fan et al, 2008; Yang et al, 2008). Overall, these results show that LOXL1 is a major gene associated with XFS.…”

Section: Introductionmentioning

confidence: 90%

See 1 more Smart Citation

Association of clusterin (CLU) variants and exfoliation syndrome: An analysis in two Caucasian studies and a meta-analysis

Fan

Pasquale

Kang

et al. 2015

Experimental Eye Research

View full text Add to dashboard Cite

Exfoliation syndrome (XFS) is an important risk factor for glaucoma (XFG) worldwide. LOXL1 variants are highly associated with XFS in most populations; however, the high frequency of risk alleles in normal individuals and the reversal of risk alleles in different ethnic populations suggest that other factors contribute to XFS pathogenesis. Clusterin (CLU) is an extracellular matrix chaperone that prevents protein aggregation and is highly expressed in ocular tissues affected by XFS. Studies examining common CLU variants for association with XFS have been inconsistent. The purpose of this study was to evaluate CLU variants for association with XFS in two independent datasets from the United States (222 cases and 344 controls) and Israel (92 cases and 102 controls). Seven tag SNPs that captured >95% of alleles at r2 greater than 0.8 across the CLU genomic region were genotyped using TaqMan assays. Genotypes for an additional SNP, rs2279590, were imputed using phased haplotypes of HapMap reference CEU samples. Of the 8 CLU SNPs selected for the study, none were significantly associated with XFS in either case-control group (age and sex adjusted P > 0.14 and 0.36, respectively, in the US and Israeli datasets), or when they were meta-analyzed together (age and sex adjusted P > 0.13). Haplotype analysis using all 8 SNPs or only the promoter region SNPs also did not show significant associations of CLU with XFS in the combined US and Israeli dataset (P > 0.28). Meta-analysis of the data from this study and previous studies in Caucasian populations (1,184 cases and 978 controls) resulted in statistically significant association of rs2279590 with XFS (summary OR = 1.18, 95% CI: 1.03-1.33, P = 0.01). Significant association between rs2279590 and XFS was also found in Indian populations (summary OR = 0.76, 95% CI: 0.61-0.96; P = 0.02); however, significant heterogeneity between the Caucasian and Indian populations possibly due to reversal of the risk allele precluded an overall meta-analysis for rs2279590 (Q = 0.001, I2 = 91%). No significant association was identified for rs3087554 in either Caucasian populations (summary OR = 0.90, 95% CI: 0.77-1.05, P = 0.17) or Indian populations (summary OR = 0.89, 95% CI: 0.72-1.10, P = 0.28), or in both populations combined (1,705 cases and 3,713 controls; summary OR = 0.90, 95% CI: 0.79-1.01, P = 0.08). Significant heterogeneity precluded the addition of the Japanese data to the meta-analysis for rs3087554 (Q = 0.006, I2 = 87%). Our results suggest that common CLU variants may contribute to modest XFS risk but even larger datasets are required to confirm these findings.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 90%

Association of clusterin (CLU) variants and exfoliation syndrome: An analysis in two Caucasian studies and a meta-analysis

Fan

Pasquale

Kang

et al. 2015

Experimental Eye Research

View full text Add to dashboard Cite

show abstract

“…31 We speculate that accumulation of XFM in the walls of digital precapillary arterioles or in nailfold capillaries produces nontubular vascular lumens that alter local hemodynamics and contribute to the tortuosity, hemorrhaging, and avascularity observed in this study. Furthermore, as elastin insulates all blood vessels in the body, insufficient elastogenesis due to altered lysyl oxidase-like 1 (LOXL1) expression 32 (strongly implicated in XFS/XFG 33,34 ) may also contribute to microvascular morphological changes. Interestingly, iris fluorescein angiography in LOXL1 knockout mice demonstrates leakage into the anterior chamber, 35 and canine carotid arteries exposed to elastase exhibit marked tortuosity.…”

Section: Discussionmentioning

confidence: 99%

Nailfold capillary morphology in exfoliation syndrome

Cousins

Kang

Bovee

et al. 2017

Eye

View full text Add to dashboard Cite

Purpose The purpose of the study was to investigate nailfold microvascular morphology in exfoliation syndrome with or without glaucoma (XFS/XFG) compared with primary open-angle glaucoma (POAG) and control subjects using nailfold capillary videomicroscopy. Patients and methods We used a JH-1004 capillaroscope to perform nailfold capillary videomicroscopy on the fourth and fifth digit of the non-dominant hand. We enrolled 56 XFS/XFG patients, 87 POAG patients, and 75 control subjects. Masked observers graded the videos for hemorrhages, avascular zones ≥ 200 microns (μm), and degree of microvascular tortuosity on a four-point subjective scale. Multivariable odds ratios, 95% confidence intervals and P-for trends for assessing the relation between morphological changes and POAG or XFS/XFG were obtained from logistic regression analyses. We also assessed this relation with XFS/XFG compared with POAG in multivariable models. Results After adjusting for multiple covariates, nailfold hemorrhages, avascular zones ≥ 200 μm, and higher degree of vascular tortuosity were more common in XFS/XFG vs controls (P-for trend ≤ 0.0001) and in POAG vs controls (P-for trend ≤ 0.01). For each 100 capillaries, the number of hemorrhages was similar (P-for trend = 0.91) between XFS/XFG and POAG patients; however, there were more avascular zones per 100 capillaries with borderline significance (P-for trend = 0.04) in the XFS/XFG group. XFS/XFG patients had more tortuosity than POAG patients; specifically, having a tortuosity score ≥ 1.5 was associated with a 4.4-fold increased odds of XFS/XFG (95% confidence interval: 1.5-13.3) relative to a tortuosity score o1.0 (P-for trend = 0.005). Conclusion A high degree of nailfold capillary tortuosity is a distinct non-ocular feature associated with XFS/XFG compared with either POAG or controls.

show abstract

“…Previous meta-analyses on the same topic included fewer studies (Chen et al, 2010;N = 25;Tang et al, 2014;N = 12;Wang et al, 2014;N = 25;Ji et al, 2015;N = 33). More importantly, they provided results on fewer ethnic groups because of limited data at the time of the literature search (Chen et al, 2010;Wang et al, 2014) or because of different eligibility criteria and the use of broad categories to define ethnicity (Tang et al, 2014;Ji et al, 2015). With 39 independent cohorts included in the analyses we were able to synthesize data (at least two independent studies per ethnic group) for Caucasians, Japanese, Koreans, Chinese, South Asians, Middle Easterners, and Black South Africans.…”

Section: Discussionmentioning

confidence: 95%

“…The purpose of this study was to conduct a meta-analysis of published data on the association of LOXL1 polymorphisms rs3825942, rs1048661, and rs2165241 with PEX (with or without glaucoma) in different ethnic groups. Although there have been previous meta-analyses on this topic (Chen et al, 2010;Tang et al, 2014;Wang et al, 2014;Ji et al, 2015), additional data have emerged, which allow for subgroup analyses in a larger number of well-defined ethnic groups. In addition, the present work explores heterogeneity between studies and associated factors, investigates possible sources of bias, including publication bias, and assesses the quality of study methodology and the genetic quality of individual studies.…”

Section: Introductionmentioning

confidence: 93%

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

View full text Add to dashboard Cite

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.

show abstract

LOXL1 Gene Polymorphism With Exfoliation Syndrome/Exfoliation Glaucoma

Abstract: Our meta-analysis indicates that rs1048661 ("G" alleles) had weak association with XFG/XFS; rs3825942 ("G" alleles) had strongly association with XFG/XFS; and rs2165241("T" alleles) had significant risk with XFG/XFS in some ethnicity.

Cited by 36 publications

References 45 publications

Association of clusterin (CLU) variants and exfoliation syndrome: An analysis in two Caucasian studies and a meta-analysis

Association of clusterin (CLU) variants and exfoliation syndrome: An analysis in two Caucasian studies and a meta-analysis

Nailfold capillary morphology in exfoliation syndrome

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

Contact Info

Product

Resources

About