EPHA2 Polymorphisms and Age-Related Cataract in India

PLOS ONE, Dec 2019

Objective We investigated whether previously reported single nucleotide polymorphisms (SNPs) of EPHA2 in European studies are associated with cataract in India. Methods We carried out a population-based genetic association study. We enumerated randomly sampled villages in two areas of north and south India to identify people aged 40 and over. Participants attended a clinical examination including lens photography and provided a blood sample for genotyping. Lens images were graded by the Lens Opacification Classification System (LOCS III). Cataract was defined as a LOCS III grade of nuclear ≥4, cortical ≥3, posterior sub-capsular (PSC) ≥2, or dense opacities or aphakia/pseudophakia in either eye. We genotyped SNPs rs3754334, rs7543472 and rs11260867 on genomic DNA extracted from peripheral blood leukocytes using TaqMan assays in an ABI 7900 real-time PCR. We used logistic regression with robust standard errors to examine the association between cataract and the EPHA2 SNPs, adjusting for age, sex and location. Results 7418 participants had data on at least one of the SNPs investigated. Genotype frequencies of controls were in Hardy-Weinberg Equilibrium (p>0.05). There was no association of rs3754334 with cataract or type of cataract. Minor allele homozygous genotypes of rs7543472 and rs11260867 compared to the major homozygote genotype were associated with cortical cataract, Odds ratio (OR) = 1.8, 95% Confidence Interval (CI) (1.1, 3.1) p = 0.03 and 2.9 (1.2, 7.1) p = 0.01 respectively, and with PSC cataract, OR = 1.5 (1.1, 2.2) p = 0.02 and 1.8 (0.9, 3.6) p = 0.07 respectively. There was no consistent association of SNPs with nuclear cataract or a combined variable of any type of cataract including operated cataract. Conclusions Our results in the Indian population agree with previous studies of the association of EPHA2 variants with cortical cataracts. We report new findings for the association with PSC which is particularly prevalent in Indians.

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EPHA2 Polymorphisms and Age-Related Cataract in India

Citation: Sundaresan P, Ravindran RD, Vashist P, Shanker A, Nitsch D, et al. ( EPHA2 Polymorphisms and Age-Related Cataract in India Periasamy Sundaresan 0 Ravilla D. Ravindran 0 Praveen Vashist 0 Ashwini Shanker 0 Dorothea Nitsch 0 Badrinath Talwar 0 Giovanni Maraini 0 Monica Camparini 0 Bareng Aletta S. Nonyane 0 Liam Smeeth 0 Usha Chakravarthy 0 James F. Hejtmancik 0 Astrid E. Fletcher 0 Roy A. Quinlan, University of Durham, United Kingdom 0 1 Department of Genetics, Dr. G. Venkataswamy Eye Research Institute, Aravind Medical Research Foundation, Aravind Eye Hospital , Madurai, Tamil Nadu , India , 2 Aravind Eye Hospital , Pondicherry , India , 3 Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences , New Delhi , India , 4 Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine , London , United Kingdom , 5 Dipartimento di Scienze Otorino-Odonto-Oftalmologiche e Cervico Facciali, Sezione di Oftalmologia, Universita` degli Studi di Parma , Parma , Italy , 6 School of Medicine, Dentistry and Biomedical Sciences, Centre for Vision and Vascular Science, Queen's University Belfast, United Kingdom, 7 Section on Ophthalmic Molecular Genetics, National Eye Institute , Bethesda, Maryland , United States of America Objective: We investigated whether previously reported single nucleotide polymorphisms (SNPs) of EPHA2 in European studies are associated with cataract in India. Methods: We carried out a population-based genetic association study. We enumerated randomly sampled villages in two areas of north and south India to identify people aged 40 and over. Participants attended a clinical examination including lens photography and provided a blood sample for genotyping. Lens images were graded by the Lens Opacification Classification System (LOCS III). Cataract was defined as a LOCS III grade of nuclear $4, cortical $3, posterior sub-capsular (PSC) $2, or dense opacities or aphakia/pseudophakia in either eye. We genotyped SNPs rs3754334, rs7543472 and rs11260867 on genomic DNA extracted from peripheral blood leukocytes using TaqMan assays in an ABI 7900 real-time PCR. We used logistic regression with robust standard errors to examine the association between cataract and the EPHA2 SNPs, adjusting for age, sex and location. Results: 7418 participants had data on at least one of the SNPs investigated. Genotype frequencies of controls were in Hardy-Weinberg Equilibrium (p.0.05). There was no association of rs3754334 with cataract or type of cataract. Minor allele homozygous genotypes of rs7543472 and rs11260867 compared to the major homozygote genotype were associated with cortical cataract, Odds ratio (OR) = 1.8, 95% Confidence Interval (CI) (1.1, 3.1) p = 0.03 and 2.9 (1.2, 7.1) p = 0.01 respectively, and with PSC cataract, OR = 1.5 (1.1, 2.2) p = 0.02 and 1.8 (0.9, 3.6) p = 0.07 respectively. There was no consistent association of SNPs with nuclear cataract or a combined variable of any type of cataract including operated cataract. Conclusions: Our results in the Indian population agree with previous studies of the association of EPHA2 variants with cortical cataracts. We report new findings for the association with PSC which is particularly prevalent in Indians. - Funding: This work was supported by Wellcome Trust UK grants 073300 and G082571. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. Age-related cataract results from increasing opacification of the ocular lens eventually leading to visual loss and is a problem found in many people throughout the world as they age. Surgery with intraocular lens implantation is currently the only effective procedure. In low income countries with poor access to cataract surgery, cataract is the main cause of vision impairment and blindness [1]. In well-resourced countries cataract surgery is one of the highest health care expenditures [2]. There is evidence of a genetic component to age-related cataract. Earlier studies found that family history was a risk factor for cataract [36] while the strongest evidence came from twin studies demonstrating a heritability of 48% for nuclear cataract [7] and 59% for cortical cataract [8]. Most work on cataract genetics has focused on inherited congenital cataract and there has been limited success in identifying common genetic variants associated with age-related cataract. However recently, some genetic variants in populations of European descent have been found to be associated with cataract, primarily cortical cataract [912]. We aimed to establish if these variants confer the same risk in Indians. The prevalence of cataract in the Indian population has been found to be particularly high, even when the level of cataract surgery is taken into account, and cataract occurs at a younger age than in Weste (...truncated)


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Periasamy Sundaresan, Ravilla D. Ravindran, Praveen Vashist, Ashwini Shanker, Dorothea Nitsch, Badrinath Talwar, Giovanni Maraini, Monica Camparini, Bareng Aletta S. Nonyane, Liam Smeeth, Usha Chakravarthy, James F. Hejtmancik, Astrid E. Fletcher. EPHA2 Polymorphisms and Age-Related Cataract in India, PLOS ONE, 2012, Volume 7, Issue 3, DOI: 10.1371/journal.pone.0033001