No abstract

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.

The precise etiology and reasons for the increase in incidence of autoimmune disorders still remain unclear, and although both genetic and environmental factors have been proven to shape individual predisposition, it is not known which of the factors, if not both, is responsible for the boom observed during the last decades. In order to establish whether a higher frequency of autoimmune-predisposing alleles may explain this increase we took advantage of ancient DNA methodology to establish the genetic predisposition, conferred by cytotoxic T lymphocyte associated antigen-4 (CTLA4) +49A/G and human leukocyte antigens (HLA) DQB1(57), in population inhabiting Poland in the Middle Ages. After successful typing of 42 individuals from a 12th approximately 14th's century archeological burial site, we found that frequencies of the predisposing alleles in the medieval population were higher than they are at present, suggesting thus that the recently observed incidence increase results most probably from factors of other than genetic nature.