Mitochondrial polymorphism A10398G and Haplogroup I are associated with Fuchs' endothelial corneal dystrophy.

Published

Journal Article

PURPOSE:We investigated whether mitochondrial DNA (mtDNA) variants affect the susceptibility of Fuchs endothelial corneal dystrophy (FECD). METHODS:Ten mtDNA variants defining European haplogroups were genotyped in a discovery dataset consisting of 530 cases and 498 controls of European descent from the Duke FECD cohort. Association tests for mtDNA markers and haplogroups were performed using logistic regression models with adjustment of age and sex. Subset analyses included controlling for additional effects of either the TCF4 SNP rs613872 or cigarette smoking. Our replication dataset was derived from the genome-wide association study (GWAS) of the FECD Genetics Consortium, where genotypes for three of 10 mtDNA markers were available. Replication analyses were performed to compare non-Duke cases to all GWAS controls (GWAS1, N = 3200), and to non-Duke controls (GWAS2, N = 3043). RESULTS:The variant A10398G was significantly associated with FECD (odds ratio [OR] = 0.72; 95% confidence interval [CI] = [0.53, 0.98]; P = 0.034), and remains significant after adjusting for smoking status (min P = 0.012). This variant was replicated in GWAS1 (P = 0.019) and GWAS2 (P = 0.036). Haplogroup I was significantly associated with FECD (OR = 0.46; 95% CI = [0.22, 0.97]; P = 0.041) and remains significant after adjusting for the effect of smoking (min P = 0.008) or rs613872 (P = 0.034). CONCLUSIONS:The 10398G allele and Haplogroup I appear to confer significant protective effects for FECD. The effect of A10398G and Haplogroup I to FECD is likely independent of the known TCF4 variant. More data are needed to decipher the interaction between smoking and mtDNA haplogroups.

Full Text

Duke Authors

Cited Authors

  • Li, Y-J; Minear, MA; Qin, X; Rimmler, J; Hauser, MA; Allingham, RR; Igo, RP; Lass, JH; Iyengar, SK; Klintworth, GK; Afshari, NA; Gregory, SG; FECD Genetics Consortium,

Published Date

  • June 10, 2014

Published In

Volume / Issue

  • 55 / 7

Start / End Page

  • 4577 - 4584

PubMed ID

  • 24917144

Pubmed Central ID

  • 24917144

Electronic International Standard Serial Number (EISSN)

  • 1552-5783

International Standard Serial Number (ISSN)

  • 1552-5783

Digital Object Identifier (DOI)

  • 10.1167/iovs.13-13517

Language

  • eng