engleski

Linkage disequilibria between human leucocyte antigen-B closely linked microsatellites in the Croatian population

The aim of the present study was to investigate polymorphism of D6S2927, STR_MICA, D6S2793, TNFa (D6S2792), TNFb and TNFd (D6S2789) microsatellites and linkage disequilibria between these loci and human leucocyte antigen (HLA)-B (previously tested) for better characterisation of extended HLA haplotypes. A total of 176 healthy unrelated Croatians were studied using polymerase chain reaction amplification and electrophoresis on6%polyacrylamide gel in ALFexpress sequencer. Eight HLA-B/D6S2927 haplotypic associations (B*07/D6S2927-4, B*08/D6S2927-3, B*18/D6S2927-3, B*27/D6S2927-1, B*35/ D6S2927-5, B*38/D6S2927-4, B*51/D6S2927-2 and B*61/D6S2927-1) showed strong association (P < 0.001, D > 0.5). Among 88 different HLA-B/STR_MICA haplotypic associations, seven combinations (B*07/STR_MICA-A5.1, B*08/ STR_MICA-A5.1, B*15/STR_MICA-A5, B*18/STR_MICA-A4, B*27/STR_ MICA-A4, B*38/STR_MICA-A9 and B*51/STR_MICA-A6) demonstrated high linkage (D
0.3) with significant P value (P<0.001). Strong associations were also observed for five HLA-B/D6S2793 haplotypes (B*07/D6S2793-CA17, B*08/ D6S2793-CA24, B*13/D6S2793-CA18, B*14/D6S2793-CA14 and B*27/ D6S2793-CA14). HLA-B*08/TNFb3 and HLA-B*50/TNFb7 were the strongest associations for HLA-B/TNFb. Nine HLA-B/TNFa combinations were observed with significant P value (B*07/TNFa11, B*08/TNFa2, B*13/TNFa7, B*18/ TNFa10, B*27/TNFa6, B*37/TNFa9, B*38/TNFa10, B*39/TNFa13 and B*44/ TNFa4). Out of six HLA-B/TNFd haplotypic associations with strong D value, HLA-B*08/TNFd2 and B*37/TNFd3 showed the highest statistical significance (P < 0.0001). These results provide data on the region around the HLA-B that is very attractive because of its contribution to genetic susceptibility for many HLAassociated diseases and therefore this information will help in all further HLA-B locus–associated disease studies.

Croatians; haplotypic association; HLA-B; linkage disequilibrium; microsatellites

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