HAPLOTIPSKE VEZE DVA NAJČEŠĆA PODTIPA GENA HLA-B*27 U HRVATSKOJ POPULACIJI

Zorana Grubić, Renata Žunec, Katarina Štingl, Danijela Sviličić, Vesna Kerhin-Brkljačić

The aim of the present study was to analyze haplotypic associations of two the most common HLAB*27 subtypes (B*2702 and *2705) in the Croatian population. One hundred and eleven unrelated HLAB*27 positive individuals were included. None of them had any sign of ankylosing spondylitis. The total number of analyzed haplotypic associations was 112 because one individual was homozygous for HLA-B*27. HLA-B*27 alleles as well as HLA-A and DRB1 specificities were tested by PCR-SSP method. Among seven different HLA-B*27 alleles observed among our individuals, B*2705 was the most frequent (61.6%), followed by B*2702 (30.4%), while the frequency of all other observed alleles (B*2701, B*2703, B*2704, B*2708 i B*2714) was less than 2.0%. HLA-A*02 was the most frequent specifi city at HLA-A locus in both groups of haplotypic associations (B*2702 and B*2705) and no difference in distribution of HLAA genes was observed between two groups. Analysis of HLA-B*2702 haplotypic associations showed the high frequency of DRB1*16 (44.2%) in comparison to  B*2705 haplotypic associations (4.0%) with signifi cant P value (P<0.00001). HLA-DRB1*01 demonstrated significantly higher presence among 69 B*2705 haplotypic associations compared to 34 B*2702 haplotypic associations (28.0% vs. 1.5%; P<0.00001) .

Cilj ovog rada bio je analizirati produžene haplotipove dva najčešća podtipa gena HLA-B*27 (B*2702 i *2705) u hrvatskoj populaciji. Analizirana je skupina od 111 nesrodnih ispitanika pozitivnih za gen HLAB*27, koji do početka ovog istraživanja nisu imali nikakve simptome ankilozantnog spondilitisa. Ukupan broj praćenih haplotipskih veza bio je 112 jer je jedna osoba bila homozigot za gen HLA-B*27. Podtip gena HLA-B*27 i geni na lokusu HLA-A i -DRB1 određeni su metodom PCR-SSP kod svih ispitanika. Od 7 različitih podtipova gena HLA-B*27 uočenih među našim ispitanicima, najčešći je bio alel B*2705 (61,6%) te alel B*2702 (30,4%), dok su preostali aleli (B*2701, B*2703, B*2704, B*2708 i B*2714) uočeni jedanput, odnosno, dvaput. Najčešći gen na lokusu HLA-A bio je HLA-A*02, kako unutar haplotipskih veza alela B*2702 tako i unutar veza alela B*2705. Nije uočena razlika u zastupljenosti gena na ovom lokusu između haplotipskih veza alela B*2702 i alela B*2705. Analiza haplotipskih veza HLA-B, -DRB1 ukazala je na jaku povezanost alela B*2702 i DRB1*16 koji su se zajedno pojavili s učestalošću od 44,1%, što je statistički značajno u usporedbi s učestalošću s kojom se DRB1*16 pojavio unutar haplotipskih veza alela B*2705 (4,0%; P<0,00001). Unutar skupine od 69 haplotipskih veza alela B*2705 uočena je statistički značajno povećana učestalost HLA-DRB1*01 u usporedbi sa skupinom (N=34) haplotipskih veza alela B*2702 (28,0% naspram 1,5%; P<0,00001).