Avtor/Urednik		Štabuc-Šilih, Mirna; Ravnik-Glavač, Metka; Glavač, Damijan; Hawlina, Marko; Stražišar, Mojca
Naslov		Polymorphisms in COL4A3 and COL4A4 genes associated with keratoconus
Tip		članek
Vir		Mol Vis
Vol. in št.		Letnik 15
Leto izdaje		2009
Obseg		str. 2848-60
Jezik		eng
Abstrakt		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. Conclusion: 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. (Abstract truncated at 2000 characters)
Deskriptorji		KERATOCONUS REFRACTOMETRY EXONS POLYMERASE CHAIN REACTION POLYMORPHISM, SINGLE-STRANDED CONFORMATIONAL GENOTYPE