Naslov
Association of HLA alleles and haplotypes with CYP21A2 gene p. V282L mutation in the Croatian population

Autori
Grubic, Z. ; Maskalan, M. ; Stingl Jankovic, K. ; Zvecic, S. ; Dumic Kubat, K. ; Krnic, N. ; Zunec, R. ; Ille, J. ; Kusec, V. ; Dumic, M.

Izvornik
HLA (2059-2302) 88 (2016), 5; 239-244

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
alleles and haplotypes ; congenital adrenal hyperplasia ; human leukocyte antigen ; p.V282L mutation

Sažetak
The CYP21A2 mutations that are in linkage disequilibrium with particular HLA-A, -B, -DRB1 alleles/haplotypes, cause deficiency of the 21- hydroxylase enzyme (21-OHD) and account for the majority of congenital adrenal hyperplasia (CAH) cases. The aim of this study was to investigate those associations with the p.V282L mutation linked to the non-classical (NC) form of CAH among Croatians. The study included parents of patients with the NC form of CAH, positive for the p.V282L mutation (N = 55) and cadaveric donor samples (N = 231). All subjects were HLA-A, -B, and -DRB1 typed and tested for the presence of the p.V282L mutation. Among parents of patients, 92.73% of subjects were positive for the B*14:02 allele and almost half of them carried the HLA-A*33:01- B*14:02-DRB1*01:02 haplotype. Among cadaveric samples 77 out of 96 subjects positive for the B*14:02 allele had the p.V282L mutation. Among them, 37 were positive for the HLA-A*33:01- B*14:02-DRB1*01:02 haplotype, 23 had the HLA- A*33:01-B*14:02-DRB1*03:01 haplotype, 8 had the B*14:02-DRB1*01:02 combination and 5 were carrying the HLA-A*68:02-B*14:02-DRB1*13:03 haplotype. Only 4 of these subjects were positive for the B*14:02 allele. HLA-B*14:02 was the only single allele with association that reached statistically significant P value (RR = 12.00 ; P = 0.0024). Haplotypes B*14:02-DRB1*01:02 (P < 0.001) and HLA- A*68:02-B*14:02-DRB1*13:03 (P < 0.001) as well as HLA-A*33:01-B*14:02-DRB1*01:02 and HLA-A*33:01- B*14:02-DRB1*03:01 showed high relative risks (RR = 45.00, RR = 41.63 and RR = 36.96, respectively). Our data support the previously documented association of the HLA-A*33:01-B*14:02-DRB1*01:02 haplotype with the p.V282L mutation, but also point out a high frequency of the p.V282L mutation among Croatians with HLA-A*33:01-B*14:02- DRB1*03:01 and HLA-A*68:02-B*14:02-DRB1*13:03 haplotypes.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

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