Tags

Type your tag names separated by a space and hit enter

Polymorphisms in COL4A3 and COL4A4 genes associated with keratoconus.
Mol Vis. 2009 Dec 20; 15:2848-60.MV

Abstract

PURPOSE

Alterations in collagen type IV, alpha-3 (COL4A3) and collagen type IV, alpha-4 (COL4A4) genes may be responsible for a decrease in collagen types I and III, a feature often detected in keratoconus (KC). To evaluate the significance of alterations in COL4A3 and COL4A4 genes in KC patients, we screened both genes and estimated the significance of polymorphisms in Slovenian patients with KC.

METHODS

The study included 104 unrelated patients with KC and 157 healthy blood donors. Diagnosis was established by clinical examination, electronic refractometry, and keratometry. DNA was extracted from blood, and gene exons were amplified by PCR. Non-isotopic high-resolution single-stranded conformation analysis (SSCA) was used to screen COL4A3 and COL4A4 genes, and migration shifts detected by SSCA were subsequently sequenced. For statistical evaluation, control blood donors were chosen according to age, sex, and not having blood relationship. Neither patients nor control blood donors chosen for statistical analysis were in blood relationship. We used Fisher's exact test for statistical evaluation, with p<0.05 considered significant.

RESULTS

We detected eight polymorphisms in the COL4A3 gene and six in the COL4A4 gene. Allele differences in D326Y in COL4A3 and M1237V and F1644F in COL4A4 are significantly distinctive of KC patients (Fisher's exact test, p<0.05). When analyzing different genotypes under three models (dominant, recessive, and additive), we established that P141L, D326Y, and G895G in COL4A3 and P482S, M1327V, V1516V, and F1644F in COL4A4 have significant differences in genotype distribution between KC patients and the control group.

CONCLUSIONS

This is the first mutational screening of COL4A3 and COL4A4 genes in KC patients to establish the status of these genes and compare them to a control population. Analysis of COL4A3 and COL4A4 revealed no mutations related to KC patients, but specific genotypes of seven previously described polymorphisms are significantly associated with KC under dominant, recessive, or additive models. Differences in the expression of type IV collagen in previously published data about chromosomal instabilities in the regions in which the analyzed genes were mapped and our data indicate a probability that some of the polymorphisms we detected could be related to KC.

Authors+Show Affiliations

Eye Hospital, University Medical Centre, Ljubljana, Slovenia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20029656

Citation

Stabuc-Silih, Mirna, et al. "Polymorphisms in COL4A3 and COL4A4 Genes Associated With Keratoconus." Molecular Vision, vol. 15, 2009, pp. 2848-60.
Stabuc-Silih M, Ravnik-Glavac M, Glavac D, et al. Polymorphisms in COL4A3 and COL4A4 genes associated with keratoconus. Mol Vis. 2009;15:2848-60.
Stabuc-Silih, M., Ravnik-Glavac, M., Glavac, D., Hawlina, M., & Strazisar, M. (2009). Polymorphisms in COL4A3 and COL4A4 genes associated with keratoconus. Molecular Vision, 15, 2848-60.
Stabuc-Silih M, et al. Polymorphisms in COL4A3 and COL4A4 Genes Associated With Keratoconus. Mol Vis. 2009 Dec 20;15:2848-60. PubMed PMID: 20029656.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Polymorphisms in COL4A3 and COL4A4 genes associated with keratoconus. AU - Stabuc-Silih,Mirna, AU - Ravnik-Glavac,Metka, AU - Glavac,Damjan, AU - Hawlina,Marko, AU - Strazisar,Mojca, Y1 - 2009/12/20/ PY - 2009/07/10/received PY - 2009/12/15/accepted PY - 2009/12/24/entrez PY - 2009/12/24/pubmed PY - 2010/3/10/medline SP - 2848 EP - 60 JF - Molecular vision JO - Mol. Vis. VL - 15 N2 - PURPOSE: Alterations in collagen type IV, alpha-3 (COL4A3) and collagen type IV, alpha-4 (COL4A4) genes may be responsible for a decrease in collagen types I and III, a feature often detected in keratoconus (KC). To evaluate the significance of alterations in COL4A3 and COL4A4 genes in KC patients, we screened both genes and estimated the significance of polymorphisms in Slovenian patients with KC. METHODS: The study included 104 unrelated patients with KC and 157 healthy blood donors. Diagnosis was established by clinical examination, electronic refractometry, and keratometry. DNA was extracted from blood, and gene exons were amplified by PCR. Non-isotopic high-resolution single-stranded conformation analysis (SSCA) was used to screen COL4A3 and COL4A4 genes, and migration shifts detected by SSCA were subsequently sequenced. For statistical evaluation, control blood donors were chosen according to age, sex, and not having blood relationship. Neither patients nor control blood donors chosen for statistical analysis were in blood relationship. We used Fisher's exact test for statistical evaluation, with p<0.05 considered significant. RESULTS: We detected eight polymorphisms in the COL4A3 gene and six in the COL4A4 gene. Allele differences in D326Y in COL4A3 and M1237V and F1644F in COL4A4 are significantly distinctive of KC patients (Fisher's exact test, p<0.05). When analyzing different genotypes under three models (dominant, recessive, and additive), we established that P141L, D326Y, and G895G in COL4A3 and P482S, M1327V, V1516V, and F1644F in COL4A4 have significant differences in genotype distribution between KC patients and the control group. CONCLUSIONS: This is the first mutational screening of COL4A3 and COL4A4 genes in KC patients to establish the status of these genes and compare them to a control population. Analysis of COL4A3 and COL4A4 revealed no mutations related to KC patients, but specific genotypes of seven previously described polymorphisms are significantly associated with KC under dominant, recessive, or additive models. Differences in the expression of type IV collagen in previously published data about chromosomal instabilities in the regions in which the analyzed genes were mapped and our data indicate a probability that some of the polymorphisms we detected could be related to KC. SN - 1090-0535 UR - https://www.unboundmedicine.com/medline/citation/20029656/abstract/Polymorphisms_in_COL4A3_and_COL4A4_genes_associated_with_keratoconus_ L2 - http://www.molvis.org/molvis/v15/a301/ DB - PRIME DP - Unbound Medicine ER -