Abstract

Celiac disease is a permanent gluten intolerance strongly associated with HLA class II antigens. The over presentation of particular HLA alleles and haplotypes has been described in several populations. Different lines of evidence obtained during the last years suggest that a particular HLA-DQ heterodimer, encoded by the DQA1*0501 and DQB1*0201 genes in cis or trans conformation, confers the primary disease susceptibility. We report the HLA class II allelic distribution and DQA1/DQB1 genotypes in 62 Chilean celiac patients compared with 124 control subjects in Santiago, Chile. We found a pronounced increase of the 'susceptible' alleles: DQA1*0501 (0.480 vs 0.169, P(c) < 0.0005), DQB1*0302 (0.430 vs 0.242, P(c) = 0.002) and DQB1*0201 (0.250 vs 0.125, P(c) = 0.037) in celiac patients in comparison with control children. As for 'protective' alleles, we detected a high frequency of DQA1*0101 (0.310 vs 0.160, P(c) = 0.01), DQA1*0201 (0.105 vs 0.010, P(c) < 0.0075) and DQB1*0301 (0.250 vs 0.100, P(c) = 0.010) in controls. In relation to risk haplotypes, the main combination observed was the conformation DQ8 (DQB1*0302/DQA1*0301) over DQ2 (DQB1*0201/DQA1*0501). In conclusion, results show that celiac disease in Chilean patients is primarily associated with DQ8 conformation. This is concordant with the high frequency of DR4 alleles (in linkage disequilibrium with DQB1*0302) detected in Amerind groups in Chile, where DQB1*0302 is more frequent than DQB1*0201.