Galactokinase gene mutations and age-related cataract. Lack ofassociation in an Italian population

[摘要] Purpose: To investigate possible associations between sequencechanges in the galactokinase gene (GALK1) and age-related cataractin a European population.Methods: Persons without lens opacities and persons with clinicallysignificant age-related cataract were selected from those participatingin the Collaborative Italian-American Clinical Trial of NutritionalSupplements and Age-Related Cataract or from those attending the Sectionof Ophthalmology of the University of Parma for cataract surgery. Typeand severity of the opacities were assessed by slit-lamp andretro-illumination lens photographs. Mutations in GALK1 wereidentified by PCR amplification of individual exons and flankingsequences and sequencing using fluorescent terminator technology in anABI 377 Prism or 3100 automated DNA sequencer.Results: DNA samples were obtained from 115 individuals with clearlenses and from 185 individuals with cataract (106 with any nuclear, 88with any cortical, and 25 with any posterior sub capsular cataract). 157of the 185 patients with cataract (85%) were age-matched with a controlwithin an age range of plus or minus 1 year. SNPs causing amino acidchanges in the galactokinase protein were identified in exon 4; I184M,1/115 control versus 0/185 cataractous individuals, p=0.38, exon 6;G274D, 0/115 control versus 1/185 cataractous individuals, p>0.99,and exon 7; V338A, 0/115 control versus 1/185 cataractous individuals,p>0.99. Thus, there were no significant differences in thedistribution of sequence alterations resulting in amino acid changesbetween control and cataractous individuals. Eighty samples showed a Cto T transition 43 bases into intron 7 (46 cataracts and 34 controls).Testing the distribution of the intron 7 findings showed Hardy-Weinbergequilibrium for both cases (p=0.73) and controls (p=0.51). There was nodifference in C/T distribution between cases and controls (p=0.27).Conclusions: In this northern Italian population age-relatedcataract does not appear to be associated with GALK1 alleles. Sincethis is due to a lack of sequence changes in both affected and controlindividuals, this study cannot rule out the possibility of anassociation in other populations.

[学科分类] 生物化学/生物物理