Changes in frequency of IDDM-associated HLA DQB, CTLA4 and INS alleles

The incidence of type 1 diabetes is increasing worldwide. In Poland, the number of cases tripled during the last two decades. The aim of this study was to test the hypothesis that the increase may be at least partly explained by a shift in predisposing alleles' frequencies - resulting from treating the otherwise lethal disease, generally better health care as well as selective pressure imposed by pathogens affecting humankind throughout history. The source of DNA was skeletal remains of 232 individuals excavated in four burial sites, dating back to 11th-14th centuries. With all necessary precautions required in ancient DNA analysis, frequencies of HLA DQB(57), CTLA4+49A/G and INS -23A/T alleles were assessed and compared with available data, characterising contemporary Polish population. Frequency of HLA DQB(57-Asp) protective allele is much higher in present-day population of Poland (50.6%) than in the group of 155 medieval specimens successfully typed for this polymorphism (28.4%, P < 0.001). Out of 86 medieval individuals typed for CTLA4+49A/G, 29.1% were homozygous for the predisposing G allele, which is significantly more than contemporarily - 7.6% (P < 0.001). No statistically significant difference was found in alleles and genotypes frequencies of INS-23A/T polymorphic site. Contrary to the initial assumptions, genetic predisposition towards type 1 diabetes, conferred by HLA DQB(57), CTLA4+49A/G and INS -23A/T alleles is much lower contemporarily than it was approximately 700 years before present. This suggests involvement of other than genetic factors in the fast growing incidence of the disease.