Confirmation of susceptibility gene loci on chromosome 1 in Northern ChinaHan families with type 2 diabetes

Objective To confirm previous effort to identify type 2 diabetes susceptibi lity genes in a Northern Chinese population by conducting a new genome scan with both an increased number of type 2 diabetes families and a new set of microsatellite markers within the previously localized regions. Methods A genome scan method was applied. After multiplexed PCR, electropho reses, genescan and genotyping analysis, we obtained size information for a ll loci, and then a further study was done by both parametric and non-param etric linkage analysis to investigate the P values and Z values of these lo ci. Results We surveyed 34 microsatellite markers which distributed within 5 re gions along chromosome 1, and a total of 12 000 genotypes were screened. Ev idence of linkage with diabetes was identified for 8 of the 34 loci. All P values of the 8 loci were lower than 0.05, and the highest Z value was 2.17 . A very interesting finding is that all 5 markers at the p- terminal 1p36. 3-1p36.23 region, spanning a long range of 16.9 cM, were identified to have a low P value of less than 0.05, which suggests that this region may conta in multiple susceptibility genes. Regions 4 and 5 also confirmed the previo us findings, and we narrowed these two regions to a 2.7 cM and 2.5 cM regio ns, respectively. Conclusions We further confirmed the results gained in the previous genome- wide scan using an increased number of NIDDM families and a new set of micr osatellite markers lying within the initially localized regions. The fact t hat all 5 loci at the p- terminal region displayed a low P value of less th an 0.05 suggests that more than 1 susceptibility gene may reside in this re gion.