THE INSULIN GENE REGION AND SUSCEPTIBILITY TO INSULIN-DEPENDENT DIABETES-MELLITUS IN 4 RACES - NEW INSIGHTS FROM AFRO-CARIBBEAN RACE-SPECIFIC HAPLOTYPES

The IDDM2 component of the genetic susceptibility to insulin-dependent diabetes mellitus (IDDM) has been mapped to chromosome 11p15.5, The e xact identity of IDDM2 remains uncertain. It has been suggested that I DDM2 maps within the 5' VNTR (variable number tandem repeat) polymorph ism upstream of the insulin gene (INS), This has not been confirmed an d a contribution from other INS gene region polymorphisms cannot be ex cluded, We present INS region genotype data from four racial groups: t he Japanese, Hong Kong Chinese, North Indian Asians and Afro-Caribbean s (two groups; one born and resident in the UK, one in Jamaica). These races have not been previously studied with the range of INS region p olymorphisms included here. No INS polymorphism was associated with ID DM across all races. These data from this study thus do not identify a ny INS polymorphism as IDDM2. The Afro-Caribbean race showed a very di fferent distribution of INS genotypes from the other races and novel r ace-specific INS haplotypes were identified. Analysis of these exclude d a contribution to susceptibility to IDDM from the- 23HphI INS polymo rphism. An Afro-Caribbean INS haplotype which differed only at the VNT R from the very protective INS haplotype (VPH) identified in white Cau casians was detected, Population analysis of this haplotype will allow direct assessment of the role of the VNTR in susceptibility to IDDM, In conclusion, the diverse Afro-Caribbean TH/INS/IGF2 haplotypes ident ified in this study will be valuable in mapping IDDM2 more precisely.