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Reply to NRM Buist

Division of Preventive Medicine Brigham and Women's Hospital Harvard Medical School 900 Commonwealth Avenue East Boston, MA 02215

Correspondence: E-mail: dschaumberg{at}rics.bwh.harvard.edu

Dear Sir:

Buist suggests that the increased risk of cataract we observed among taller men in our study (1) may be of genetic origin and specifically related to Stickler syndrome. The incidence of Stickler syndrome, a mild autosomal dominant chondrodysplasia primarily due to a mutation in the COL2A1 gene, is not known but may approach 1 in 10000 births (2). As we stated in our article, given the familial clustering of nuclear and cortical lens opacities observed in other studies (3, 4), we do consider genetic susceptibility to be one plausible explanation for our finding. However, several factors argue against the suggestion that Stickler syndrome alone or together with other genetic syndromes per se may explain the relation of height with cataract.

We attempted to include only age-related cataracts as endpoints in our study; therefore, we excluded cataracts occurring in subjects with a genetic syndrome known to be associated with cataract. Although we could not exclude cataracts among participants with an unrecognized cataract-associated genetic syndrome, this number is likely to have been far too small to have substantially affected our findings. In addition, Stickler syndrome is associated with cortical lens opacities (5), whereas we found an association primarily with nuclear cataract. We think it is more likely that rather than being associated with any particular genetic syndrome or genetic mutation, the relation of height with cataract has to do with common genetic codeterminants of height and cataract, if genes are involved at all. Furthermore, given the strong evidence from animal studies that energy restriction results in a lower incidence of cataract (6), we would certainly not rule out the possibility that variations in nutrition could influence the relation observed between taller stature and increased risk of age-related cataract in men.

REFERENCES

1. Schaumberg DA, Glynn RJ, Christen WG, Hankinson SE, Hennekens CH. Relations of body fat distribution and height with cataract in men. Am J Clin Nutr 2000;72:1495–502.[Abstract/Free Full Text]
2. Vandenberg P. Molecular basis of heritable connective tissue disease. Biochem Med Metab Biol 1993;49:1–12.[Medline]
3. Heiba IM, Elston RC, Klein BE, Klein R. Genetic etiology of nuclear cataract: evidence for a major gene. Am J Med Genet 1993;47:1208–14.[Medline]
4. Hammond CJ, Snieder H, Spector TD, Gilbert CE. Genetic and environmental factors in age-related nuclear cataracts in monozygotic and dizygotic twins. N Engl J Med 2000;342:1746–90.
5. Snead MP, Yates JRW. Clinical and molecular genetics of Stickler syndrome. J Med Genet 1999;36:353–9.[Abstract/Free Full Text]
6. Taylor A, Lipman RD, Jahngen-Hodge J, et al. Dietary calorie restriction in the Emory mouse: effects on lifespan, eye lens cataract prevalence and progression, levels of ascorbate, glutathione, glucose, and glycohemoglobin, tail collagen breaktime, DNA and RNA oxidation, skin integrity, fecundity, and cancer. Mech Ageing Dev 1995;79:33–57.[Medline]

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