Genetic susceptibility to fibrocalculous pancreatic diabetes in Bangladeshi subjects: a family study

Abstract

Fibrocalculous pancreatic diabetes (FCPD) is an uncommon cause of diabetes, seen mainly in developing countries. A family-based study was carried out in 67 Bangladeshi families, consisting of a proband with FCPD and both parents, to determine whether an association exists between FCPD susceptibility and either the major histocompatiblity complex (MHC) or insulin gene (INS) loci. HLA-DQB1 typing was done using allele-specific primers, and INS was typed using the restriction enzyme HphI. Three microsatellites (TNFa, TNFc and TNFd), from within and flanking the TNF-LT locus, were used for MHC Class IV typing and a PCR-RFLP assay was used to define the -308G/A TNF promoter polymorphism. The extended transmission disequilibrium test (ETDT) was used for statistical analysis. An overall association was observed between FCPD and HLA-DQB1 (P = 0.003), that was largely due to a positive association with HLA-DQB1*0302 and a negative association with HLA-DQB1*0202. Although no association was found between FCPD and TNF-LT microsatellite markers a trend was observed for TNFc (P = 0.037, Pc = 0.15). No association was found between FCPD and INS (P = 0.26). This study confirms an association between FCPD and the MHC using a family-based study design and the stringent ETDT analysis; a novel protective association was found with HLA-DQB1*0202 in Bangladeshi FCPD subjects. The genetic susceptibility to FCPD has features both similar and dissimilar to T1DM.