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Genetic association of COL5A1 variants in keratoconus patients suggests a complex connection between corneal thinning and keratoconus.
Monday,2013-09-30 17:32 America/Los_Angeles — poolea2
| Title | Genetic association of COL5A1 variants in keratoconus patients suggests a complex connection between corneal thinning and keratoconus. |
| Publication Type | Journal Article |
| Year of Publication | 2013 |
| Authors | Li, X, Bykhovskaya, Y, Canedo, ALaura Caia, Haritunians, T, Siscovick, D, Aldave, AJ, Szczotka-Flynn, L, Iyengar, SK, Rotter, JI, Taylor, KD, Rabinowitz, YS |
| Journal | Invest Ophthalmol Vis Sci |
| Volume | 54 |
| Issue | 4 |
| Pagination | 2696-704 |
| Date Published | 2013 Apr 12 |
| ISSN | 1552-5783 |
| Keywords | Adult, Aged, Collagen Type V, Cornea, Corneal Topography, DNA, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Keratoconus, Male, Microscopy, Acoustic, Middle Aged, Polymorphism, Single Nucleotide, Tomography, Optical Coherence |
| Abstract | <p><b>PURPOSE: </b>Single nucleotide polymorphisms (SNPs) located near or within the COL5A1 gene, at 9q34.2-q34.3 chromosomal region have been reported in association with central corneal thickness (CCT). Using family linkage analysis, we identified a keratoconus susceptibility locus at 9q34. These findings led us to perform an association study between COL5A1 variation and keratoconus susceptibility.</p><p><b>METHODS: </b>A Caucasian case-control cohort of 222 keratoconus patients and 3324 controls was selected as the discovery panel. An independent case-control panel of 304 cases and 518 controls and a family panel of 186 subjects were replicated for genotyping and association. Forty-four SNPs (21 for discovery and 23 for fine-mapping) spanning 300 kilobases in and around COL5A1 were genotyped and tested for genetic association. Logistic regression models implemented in PLINK were used to test for association in case controls. Generalized estimating equation models accounting for familial correlations implemented in genome-wide interaction analyses with family data were used for association testing in families.</p><p><b>RESULTS: </b>Two CCT associated SNPs (rs1536482 and rs7044529 near and within COL5A1) were identified in the keratoconus discovery cohort (P values of 6.5 × 10(-3) and 7.4 × 10(-3)). SNP rs1536482 was replicated in the second case-control sample (P = 0.02), and SNP rs7044529 was replicated in a keratoconus family panel (P = 0.03). Meta P values of rs1536482 and rs7044529 in the keratoconus cohorts were 1.5 × 10(-4) (odds ratio [OR] = 1.30) and 2.9 × 10(-3) (OR = 1.39). After Bonferroni correction, the association of SNP rs1536482 remained significant (P = 6.5 × 10(-3)).</p><p><b>CONCLUSIONS: </b>SNPs in the COL5A1 region, which regulate normal variation in CCT, may play a role in the thinning associated with keratoconus.</p> |
| DOI | 10.1167/iovs.13-11601 |
| Alternate Journal | Invest. Ophthalmol. Vis. Sci. |
| PubMed ID | 23513063 |
| PubMed Central ID | PMC3630822 |
| Grant List | UL1 RR033176 / RR / NCRR NIH HHS / United States UL1RR033176 / RR / NCRR NIH HHS / United States UL1TR000124 / TR / NCATS NIH HHS / United States NEI 09052 / / PHS HHS / United States R01 AG015928 / AG / NIA NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States HL085251 / HL / NHLBI NIH HHS / United States HL105756 / HL / NHLBI NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States R01 HL085251 / HL / NHLBI NIH HHS / United States R56 AG020098 / AG / NIA NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States AG-20098 / AG / NIA NIH HHS / United States HL087652 / HL / NHLBI NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States AG-027058 / AG / NIA NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States N01-HC-55222 / HC / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States R01 HL080295 / HL / NHLBI NIH HHS / United States R01 AG020098 / AG / NIA NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States HL080295 / HL / NHLBI NIH HHS / United States N01-HC-85239 / HC / NHLBI NIH HHS / United States AG-023629 / AG / NIA NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States R01 AG027058 / AG / NIA NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States R56 AG023629 / AG / NIA NIH HHS / United States |