HIGHLY POLYMORPHIC PROMOTER REGIONS OF HLA DQA1 AND DQB1 GENES DO NOTHELP TO FURTHER DEFINE DISEASE SUSCEPTIBILITY IN INSULIN-DEPENDENT DIABETES-MELLITUS

HLA DQA1, HLA DQB1 genes confer susceptibility to insulin-dependent (t ype 1) diabetes mellitus (IDDM). Since variants of their upstream regu latory regions are linked to the exons, we investigated their promoter polymorphisms (QAP and QBP) by a combination of PCR-based typing prot ocols in 136 IDDM patients, 167 controls and 6 families with an IDDM p roband to identify possible additional susceptibility markers. Of majo r interest for IDDM susceptibility are the promoter ''splits'' of HLA DQA10301 (QAP3.1 and QAP3.2) and HLA DQB1*0302 (QBP3.2 and QBP3.3). Q AP 3.1 (96% in patients vs 98% in controls) and QBP3.2 (100% vs 99%) w ere found to be the most frequent promoter variants for HLA DQA10301 and DQB10302, respectively, whereas QAP3.2 and QBP3.3 were very rare. Furthermore the promoter ''splits'' were equally distributed on the r espective exon alleles in all groups and cosegregated in families as e xpected. In conclusion, HLA DO-mediated susceptibility and protection in IDDM is not restricted to the exon but extends to the promoter regi on without further defining the genetic risk.