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Invest Ophthalmol Vis Sci. 2014 Jun 10;55(7):4577-84. doi: 10.1167/iovs.13-13517.

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

Author information

1
Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina, United States Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North Carolina, United States.
2
Duke Molecular Physiology Institute, Duke University Medical Center, Durham, North Carolina, United States.
3
Duke Eye Center, Duke University Medical Center, Durham, North Carolina, United States.
4
Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, United States.
5
Duke Eye Center, Duke University Medical Center, Durham, North Carolina, United States Department of Pathology, Duke University Medical Center, Durham, North Carolina, United States.
6
Duke Eye Center, Duke University Medical Center, Durham, North Carolina, United States Shiley Eye Center, University of California San Diego, La Jolla, California, United States.

Abstract

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.

KEYWORDS:

TCF4; genetic association; mitochondrial haplogroup; oxidative stress; smoking

PMID:
24917144
PMCID:
PMC4109404
DOI:
10.1167/iovs.13-13517
[Indexed for MEDLINE]
Free PMC Article

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