Myopia and polymorphisms in genes for matrix metalloproteinases.

PURPOSE: To investigate the relation between myopia and variations in three genes coding for matrix metalloproteinases, enzymes that degrade matrix proteins and modulate scleral extensibility. METHODS: Three hundred sixty-six men and women, from Sheffield, United Kingdom, were genotyped for the 1G/2G polymorphism in the MMP-1 gene, the 5A/6A polymorphism in the MMP-3 gene and the Arg-->Gln polymorphism in exon 6 of the MMP-9 gene and assessed for refractive error. RESULTS: Risk of myopia was increased in people homozygous for the 5A allele of the MMP-3 gene (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.1-9.0) compared to those who were homozygous for the 6A allele, and in people homozygous for the Gln allele in exon 6 of the MMP-9 gene (OR, 2.8; 95% CI, 1.1-7.0) compared to those who were homozygous for the Arg allele. People who were homozygous for the 2G allele of the MMP-1 gene had an odds ratio for myopia of 2.3 (95% CI, 0.9-6.1), compared with those who were homozygous for the 1G allele, although this relation did not reach statistical significance. Risk of myopia increased progressively with the dose of these three alleles, showing a greater than 10-fold difference across the range. CONCLUSIONS: The results suggest that common variations in three of the genes that control breakdown of matrix proteins in the sclera may contribute to the development of simple myopia.

Lutein and zeaxanthin status and risk of age-related macular degeneration.

PURPOSE: To investigate the relation between plasma concentrations of lutein and zeaxanthin and age-related macular degeneration in a group of elderly men and women. METHODS: The Wisconsin Age-Related Maculopathy Grading System was used to grade features of early and late macular degeneration in 380 men and women, aged 66 to 75 years, from Sheffield, United Kingdom. Fasting blood samples were taken to assess plasma concentrations of lutein and zeaxanthin. RESULTS: Risk of age-related macular degeneration (early or late) was significantly higher in people with lower plasma concentrations of zeaxanthin. Compared with those whose plasma concentrations of zeaxanthin were in the highest third of the distribution, people whose plasma concentration was in the lowest third had an odds ratio for risk of age-related macular degeneration of 2.0 (95% confidence interval [CI] 1.0-4.1), after adjustment for age and other risk factors. Risk of age-related macular degeneration was increased in people with the lowest plasma concentrations of lutein plus zeaxanthin (odds ratio [OR] 1.9, 95% CI 0.9-3.5) and in those with the lowest concentrations of lutein (OR 1.7, 95% CI 0.9-3.3), but neither of these relations was statistically significant. CONCLUSIONS: These findings provide support for the view that zeaxanthin may protect against age-related macular degeneration.

Relation between size at birth and risk of age-related macular degeneration.

PURPOSE: To determine whether poor fetal growth, as determined by size at birth, is associated with increased risk of age-related macular degeneration. METHODS: A total of 660 men and women born in Sheffield, United Kingdom, between 1922 and 1930 and whose size at birth was available were traced and invited to take part in the study. Of these, 392 attended for ophthalmic examination. Age-related macular degeneration in these volunteers was determined by the Wisconsin Age-Related Maculopathy Grading System. RESULTS: The mean birth weight of subjects with macular degeneration (early or late) was heavier than that of those without (7.6 lb vs. 7.3 lb, respectively; P = 0.03). After adjustment for age, gender, and risk factors for macular degeneration, a significantly increased risk of macular degeneration was found in subjects with higher birth weight (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.1-2.0 for each SD [1 lb, 5 oz] increase in birth weight). Other parameters describing size at birth showed a weaker relation or no relation with macular degeneration, but one of the measures of fetal proportion (head circumference-to-birth weight ratio) was significantly associated with risk of macular degeneration. Subjects with macular degeneration had a significantly lower head circumference-to-birth weight ratio than did those without (11.2 vs. 12.0 respectively, P = 0.01). CONCLUSIONS: The finding that age-related macular degeneration was associated with increased rather than decreased birth weight was unexpected. Failure of the developing fetus's normal brain-sparing mechanism is a possible explanation for our finding of a lower head circumference-to-birth weight ratio among subjects with macular degeneration.

Size at birth and carotid atherosclerosis in later life.

Several studies have shown that low birthweight is associated with a higher risk of stroke and coronary heart disease in later life. Increased atherogenesis may be one underlying mechanism, but few studies have examined this directly. We used duplex ultrasonography to assess the extra-cranial carotid arteries of 389 elderly men and women born and still living in Sheffield, UK, whose recorded birth measurements were available. Men and women who had weighed 6.5 lbs or less at birth had a higher risk of having carotid stenosis >30% than those who weighed over 7.5 lbs, but this trend was not statistically significant (OR 1.8, 95% CI 1.0-3.3). Women who had been lighter or who had a smaller head circumference at birth tended to have an increased intima-media thickness, but these relations ceased to be statistically significant after adjustment for gestational age and cardiovascular risk factors. In men, by contrast, an increased intima-media thickness was associated with having been heavier at birth (P=0.049) or having had a larger abdominal circumference at birth (P=0.040), after adjustment for gestational age and cardiovascular risk factors. These results provide little evidence that impaired fetal growth increases susceptibility to atherogenesis.