PMC:5985359 / 19756-21789 JSONTXT

{"project":"2_test","denotations":[{"id":"29526280-23185296-2044776","span":{"begin":708,"end":709},"obj":"23185296"},{"id":"29526280-26200491-2044777","span":{"begin":711,"end":713},"obj":"26200491"},{"id":"29526280-25298419-2044778","span":{"begin":715,"end":717},"obj":"25298419"},{"id":"29526280-24255041-2044779","span":{"begin":719,"end":721},"obj":"24255041"},{"id":"29526280-28358029-2044780","span":{"begin":1365,"end":1367},"obj":"28358029"}],"text":"A highly significant association between expansion of the CTG18.1 trinucleotide repeat (conservatively defined as ≥50 repeats) and FECD was identified (OR = 76.47; 95% CI: 47.45–123.2; p = 5.69 × 10−71) in the white European-only portion of the cohort (n = 392; Table 1). The distribution of the CTG18.1 expansion lengths among individuals affected by FECD and age-related macular degeneration (AMD), used as an ethnically matched control population for the purpose of this study, are summarized in Figures 1A and 1B and Table 1. For the AMD cohort, 4.2% (23/550) had one expanded copy (≥50 repeats) of the CTG18.1 allele, in line with reports from other unaffected populations screened for control purposes,9, 12, 13, 14 and none were found to have two expanded alleles. In contrast, 76.4% (344/450) of the FECD cohort had one or more expanded copies of the CTG18.1 allele, of which 4.0% (18/450) had bi-allelic expansions. Interestingly, male subjects had a higher incidence of expanded CTG18.1 alleles (81.6% versus 72.8% with at least one expanded allele; Table 1) and the FECD risk associated with repeat expansion at this locus was higher in males (OR = 95.04, 95% CI: 43.08–209.70, p = 1.62 × 10−29) than in females (OR = 66.78, 95% CI: 36.79–121.20, p = 2.06 × 10−43), supporting the hypothesis that interaction of this locus with gender could be important.29\nFigure 1 Expansion of CTG18.1 Is Associated with FECD in a British and Czech Cohort\n(A) Frequency histogram comparing relative distribution of CTG repeat length in Fuchs endothelial corneal dystrophy (FECD) and age-related macular degeneration (AMD) cohorts. The longest allele detected, per individual tested, is shown. In total the FECD (blue) and AMD (white) cohorts comprised 450 and 550 individuals, respectively.\n(B) Bar chart illustrating the relative frequency of individuals with both alleles non-expanded (NE/NE), one expanded allele (E/NE), or both alleles expanded (E/E) in both the FECD and AMD cohorts. Expanded alleles are defined as ≥50 CTG repeats."}