Study finds that genetic factors account for about 50% of age-related nuclear cataracts

Twin study shows that age and environment are less important risk factors for nuclear cataracts.

Issue: August 15, 2000

ByBob Kronemyer

LONDON — A study of 506 pairs of white female twins (226 monozygotic and 280 dizygotic) between the ages of 50 and 79 found that the overall heritability of nuclear cataract was 48%. Conversely, age accounted for only 38% of the variance and unique environmental effects for 14%.

“Certainly from a population basis, the study shows that genes appear to be more important than either age or environment,” said lead investigator Christopher J. Hammond, FRCOphth, the ophthalmic research fellow at the Twin Research and Genetic Epidemiology Unit at St. Thomas’ Hospital here. “But it doesn’t necessarily apply to each individual. In other words, if an individual has a cataract, we can’t say that the cataract is caused 50% by genes and 14% by the environment. There may be subgroups within that population for whom environmental factors are very important.”

The study, which was recently published in The New England Journal of Medicine, “will come as quite a surprise to most ophthalmologists because cataracts are almost inevitable with age,” Dr. Hammond said. “Most ophthalmologists tell patients that their cataracts are mainly due to age or environment such as smoking or possibly diet and antioxidants.” For many chronic age-related diseases, such as high blood pressure, “the medical community has largely thought in terms of age and environment, and very little in terms of genes. But we’re now finding increasingly, even among these late onset diseases, that genes are important.”

Dr. Hammond said that if practitioners would stop and think about it, they would realize that genetic factors are important. After all, most cataracts are extracted in patients from a wide age group: 50 to 90 years old. “Why is it that patients develop cataracts at such different ages? If it was purely age, everyone would develop cataracts at about the same age,” Dr. Hammond said.

Detecting nuclear cataract

photograph ---The women in the study were initially recruited to participate in the St. Thomas’ United Kingdom Adult Twin Registry and were unaware of any hypotheses or proposals for specific studies. It was only later that they were invited to have an eye exam. One reason the authors only used females is that cataracts have been shown to be more common in women.

For the study, the amount of nuclear cataract in the right and left eyes was determined objectively by analysis of Scheimpflug lens photographs and subjectively with the Oxford Clinical Cataract Classification and Grading System. All eight measures (four in each eye: three photographs and one subjective) were then combined into one summary measure of nuclear cataract for each woman. A univariate maximum-likelihood model was used to estimate the variance of the genetic and environmental contributions in each of the measures. Eliminating the effects of smoking (the most important environmental effect for nuclear cataracts) altered heritability by only 1%.

“It may well be that people with a particular genetic susceptibility are prone to environmental exposures,” Dr. Hammond said. For example, “some people, if they smoke, will develop a cataract. And if they don’t, they won’t.” In essence, “the sequel to our research is to find some susceptibility genes for cataracts. Then we’ll know more about the mechanisms of how cataracts are formed. At that point, we can potentially offer preventive treatments or understand more about which particular environmental factors are important for an individual. Perhaps in the future a person with a particular genetic makeup will need to take some antioxidant or some treatment that will prevent a cataract or, more likely, delay its onset and progression.”

Although the study “shows that genes are potentially more important than environment, it may well be that the environment and the genes interact in some way so that the environment is still very important,” Dr. Hammond said.

Women only

The women in the study were initially recruited to participate in the St. Thomas’ United Kingdom Adult Twin Registry and were unaware of any hypotheses or proposals for specific studies. It was only later that they were invited to have an eye exam. One reason the authors only used females is that cataracts have been shown to be more common in women. “To ensure that you are not dealing with different phenomena in men and women, you would have to evaluate equal numbers of each sex. We simply did not have that capacity,” Dr. Hammond said. Another reason the study was limited to females is that, historically, the Twin Research and Genetic Epidemiology Unit has focused on women. “It was initially founded by a rheumatologist to look at osteoporosis,” Dr. Hammond said.

Dr. Hammond and his colleagues at this time have no intention of conducting a similar cataract study using male twins.

“Genes are important in age-related cataracts,” Dr. Hammond said. Up until now, “we’ve basically treated this condition as being age related, with a bit of environment. But we need to rethink our approach and realize that genes are important. Finding those susceptibility genes may well help us in the future. It has been estimated that if you manage to delay the onset of cataracts by 10 years, up to 50% of cataract surgery currently performed may become unnecessary.”

For Your Information:

Christopher J. Hammond, FRCOphth, can be reached at Twin Research and Genetic Epidemiology Unit, St. Thomas’ Hospital, Lambeth Palace Road, London SE1 7EH, United Kingdom; (44) 207-928-9292; fax: (44) 207-922-8154; e-mail: ch@twin-research.ac.uk.

Reference:

Hammond CJ, Snieder H, Spector TD, et al. Genetic and environmental factors in age-related nuclear cataracts in monozygotic and dizygotic twins. N Engl J Med. 2000;342:1786-1790.