Variants in the 10q26 Gene Cluster (LOC387715andHTRA1) Exhibit Enhanced Risk of Age-Related Macular Degeneration along withCFHin Indian Patients

Kaur, Inderjeet; Katta, Saritha; Hussain, Avid; Hussain, Nazimul; Mathai, Annie; Narayanan, Raja; Hussain, Anjli; Reddy, Rajeev; Majji, Ajit B; Das, Taraprasad; Chakrabarti, Subhabrata

doi:10.1167/iovs.07-0560

Cited by 57 publications

(27 citation statements)

References 36 publications

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“…79 In multiple studies examining linkage disequilibrium in the 10q26 region, the HTRA1, and LOC387715 SNPs have been reported to be in almost complete linkage disequilibrium. 76,78,80 LOC387715 mRNA is detected in the human retina 35 and retinal pigment epithelium. 35,81 It encodes a 12 kilodalton (kDa) protein, which localizes to the extracellular matrix, 82 and mitochondrial outer membrane when expressed in mammalian cells.…”

Section: Discussionmentioning

confidence: 99%

Single Nucleotide Polymorphism in the Cholesterol-24S-Hydroxylase (CYP46A1) Gene and Its Association withCFHandLOC387715Gene Polymorphisms in Age-Related Macular Degeneration

Fourgeux

Dugas

Richard

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. We investigated the association of single nucleotide polymorphism (SNP) in the cholesterol-24S-hydroxylase (CY-P46A1) gene, according to CFH and LOC387715 SNPs, with age-related macular degeneration (AMD). METHODS.We enrolled 1388 AMD patients with neovascular AMD or geographic atrophy and 487 unrelated control subjects. SNPs were genotyped in the CYP46A1 (rs754203), LOC387715 (rs10490924), and CFH (rs1061170) genes. Plasma 24S-hydroxycholesterol, the metabolic product of CYP46A1, was quantified by gas chromatography-mass spectrometry using an authentic deuterated internal standard in subgroups of patients and controls. The v 2 test was used to compare categoric allelic and genotype distributions between cases and controls. The odds ratio (OR) with a 95% confidence interval (95% CI) was calculated for AMD risk, and adjusted for age and gender. Significance levels were set at P < 0.05. RESULTS.The rs754203 SNP in the CYP46A1 gene was not associated with AMD (crude OR ¼ 1.2, 95% CI ¼ 0.9-1.4, P ¼ 0.2). The crude OR for risk of AMD was 2.9 (95% CI ¼ 2.4-3.4, P < 0.0001) according to the number of rs10490924 T alleles in the LOC387715 gene, and 2.0 (95% CI ¼ 1.7-2.3, P < 0.0001) according to the number of rs1061170 C alleles in the CFH gene. After adjustment for age and gender, an OR of 2.2 (95% CI ¼ 1.1-4.1, P ¼ 0.04) was obtained for AMD cases with the C allele in the CYP46A1 gene, and carrying no risk alleles in the CFH and LOC387715 genes.CONCLUSIONS. The rs754203 C allele in the CYP46A1 gene may confer a higher risk for exudative AMD in patients who carry no risk alleles in the CFH and LOC387715 genes. Additional studies with larger sample sizes are needed in AMD subjects at no risk in CFH and LOC387715. (Invest Ophthalmol Vis Sci.

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Section: Discussionmentioning

confidence: 99%

Single Nucleotide Polymorphism in the Cholesterol-24S-Hydroxylase (CYP46A1) Gene and Its Association withCFHandLOC387715Gene Polymorphisms in Age-Related Macular Degeneration

Fourgeux

Dugas

Richard

et al. 2012

Invest. Ophthalmol. Vis. Sci.

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“…In addition to research using fi ne mapping in white and Chinese populations, 4,6,15-17 a smaller number of SNPs targeting this region examined in East Indian AMD patients also showed this tendency. Kaur et al 34 conducted an association study of East Indian AMD patients with six SNPs spanning 6.43 kb in this region and observed only four different haplotypes. 34 There are limitations to this study.…”

Section: Discussionmentioning

confidence: 99%

“…Kaur et al 34 conducted an association study of East Indian AMD patients with six SNPs spanning 6.43 kb in this region and observed only four different haplotypes. 34 There are limitations to this study. The ratio of men to women and the age distribution were different between patients and controls.…”

Section: Discussionmentioning

confidence: 99%

Haplotype analysis of the ARMS2/HTRA1 region in Japanese patients with typical neovascular age-related macular degeneration or polypoidal choroidal vasculopathy

et al. 2010

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“…37 There is also some variability, with different variants identifi ed in different populations. 38,39 However, these genetic studies suggest a role for complement and infl ammatory modulators in AMD.…”

Section: Future Targets: Complement and Infl Ammationmentioning

confidence: 99%

Treatment of age-related macular degeneration: Beyond VEGF

Miller

2010

Jpn J Ophthalmol

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Current therapy for age-related macular degeneration (AMD) shows a dramatic change from clinical practice a decade ago. While the first pharmacologic treatment, verteporfin photodynamic therapy (PDT) slowed disease progression, newer anti-vascular epithelial growth factor (VEGF) therapies have also shown vision improvement in many patients. Combination therapies (PDT + steroid + anti-VEGF) have shown some promise, particularly in certain classes of disease. Genetic studies have identified common gene variants in the complement factor H gene that confers susceptibility to AMD, and treatments targeting the complement pathway are being explored. Another area of research is directed at the components of Bruch membrane; studies of changes in the elastic fibers and collagen within Bruch may yield drug targets for prevention and halting of disease progression. Finally, studies in photoreceptor apoptosis have identified the role of cytokines, such as monocyte chemotactic protein 1, tumor necrosis factor α, and interleukin 1β, associated with photoreceptor cell death and should be pursued as potential therapies to improve vision outcomes in neovascular AMD. Today's research into the biology of AMD will lead us to better treatment and perhaps even preventive measures in the decades ahead.

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Variants in the 10q26 Gene Cluster (LOC387715andHTRA1) Exhibit Enhanced Risk of Age-Related Macular Degeneration along withCFHin Indian Patients

Abstract: The present data provided an independent validation of the association of LOC387715 and HTRA1 SNPs, along with their risk estimates among Indian patients with AMD. These associations underscore their significant involvement in AMD susceptibility, which may be useful for predictive testing.

Cited by 57 publications

References 36 publications

Single Nucleotide Polymorphism in the Cholesterol-24S-Hydroxylase (CYP46A1) Gene and Its Association withCFHandLOC387715Gene Polymorphisms in Age-Related Macular Degeneration

Single Nucleotide Polymorphism in the Cholesterol-24S-Hydroxylase (CYP46A1) Gene and Its Association withCFHandLOC387715Gene Polymorphisms in Age-Related Macular Degeneration

Haplotype analysis of the ARMS2/HTRA1 region in Japanese patients with typical neovascular age-related macular degeneration or polypoidal choroidal vasculopathy

Treatment of age-related macular degeneration: Beyond VEGF

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