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Genetic variants in a sodium-dependent vitamin C transporter gene and age-related cataract
  1. Ravilla D Ravindran1,
  2. Periasamy Sundaresan2,
  3. Tiruvengada Krishnan3,
  4. Praveen Vashist4,
  5. Giovanni Maraini5,
  6. Vijayan Saravanan2,
  7. Usha Chakravarthy6,
  8. Liam Smeeth7,
  9. Dorothea Nitsch7,
  10. Ian S Young6,
  11. Astrid E Fletcher7
  1. 1 Cataract Services, Aravind Eye Hospital, Madurai, India
  2. 2 Department of Genetics, Dr.G.Venkataswamy Eye Research Institute, Aravind Medical Research Foundation, Madurai, India
  3. 3 Cataract Services, Aravind Eye Hospital, Pondicherry, India
  4. 4 Community Ophthalmology Department, Dr.Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, Delhi, India
  5. 5 Dipartimento di Scienze Otorino-Odonto-Oftalmologiche e Cervico Facciali, Universitá degli Studi di Parma, Parma, Italy
  6. 6 Centre for Public Health, Queen's University Belfast, Belfast, UK
  7. 7 Faculty of Epidemiology & Population Health, London School of Hygiene & Tropical Medicine, London, UK
  1. Correspondence to Professor Astrid E Fletcher, Faculty of Epidemiology & Population Health, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK; astrid.fletcher{at}


Background Cataract is a major health burden in many countries and a significant problem in India. While observational studies show lower cataract risk with increasing dietary or plasma vitamin C, randomised controlled trials of supplements have been negative. Genetic variants in vitamin C transporter proteins (SLC23A1), especially rs33972313, may provide evidence on a causal association of vitamin C with cataract.

Methods We used data from a randomly selected population-based study in people aged 60 years and above in north and south India. Of 7518 sampled, 5428 (72%) were interviewed for socioeconomic and lifestyle factors, attended hospital for lens imaging and blood collection and were subsequently genotyped for rs33972313 and rs6596473. Mixed or pure types of cataract were graded by the Lens Opacity Classification System III as nuclear (2404), cortical (494) or posterior subcapsular cataract (PSC) (1026); 1462 had no significant cataract and no history of cataract surgery and 775 had bilateral aphakia/pseudophakia.

Results rs33972313 was associated with cortical (OR 2.16; 95% CI 1.34 to 3.49, p=0.002) and PSC (OR 1.68; 95% CI 1.06 to 2.65, p=0.03) but not with nuclear cataract. In analyses of pure cataracts, associations were found only between rs33972313 and pure cortical cataracts (OR 2.29; 95% CI 1.12 to 4.65, p=0.03) and with a standardised cortical opacity score. There was no association with rs6596473 and any cataract outcomes.

Conclusions Using an established genetic variant as a proxy for lifetime ascorbate concentrations, our results support a causal association of vitamin C with cataract.

  • epidemiology
  • genetics
  • lens and zonules
  • ascorbate

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  • Contributors AEF and RDR contributed to study concept and design. AEF, RDR, LS and DN contributed to the drafting of the manuscript. AEF contributed to the statistical analysis. AEF, UC, RDR, DN and LS obtained funding. RDR, PS, PV, AEF, GM, ISY and DN were involved in the administrative, technical or material support. RDR, AEF and PS supervised the study. All authors contributed to the acquisition, analysis or interpretation of data and critical revision of the manuscript for important intellectual content.

  • Funding This work was supported by the Wellcome Trust UK (grants G073300 and G082571). The funding source had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript and decision to submit the manuscript for publication.

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval The Indian Council for Medical Research, Research Ethics Committees of the All India Institute of Medical Sciences, Aravind Eye Hospital, London School of Hygiene and Tropical Medicine and Queen’s University Belfast.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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