Genetic susceptibility to fibrocalculous pancreatic diabetes in Bangladeshi subjects: a family study.
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.
Chowdhury
Z Md
ZM
Bangladesh Institute of Research and Rehabilitation in Diabetes (BIRDEM), Endocrine and Metabolic Disorders, Dhaka 1000, Bangladesh.
McDermott
M F
MF
Davey
S
S
Hassan
Z
Z
Sinnott
P J
PJ
Hemmatpour
S K
SK
Sherwin
S
S
Ali
L
L
Aganna
E
E
Allotey
R A
RA
North
B V
BV
Cassell
P G
PG
Azad Khan
A K
AK
Hitman
G A
GA
D001459:Bangladesh; D002137:Calculi / Q000235:genetics*; D003920:Diabetes Mellitus / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006239:Haplotypes; D006650:Histocompatibility Testing; D006801:Humans; D015810:Linkage Disequilibrium; D008233:Lymphotoxin-alpha / Q000235:genetics; D008285:Major Histocompatibility Complex; D008297:Male; D018895:Microsatellite Repeats; D010195:Pancreatitis / Q000235:genetics*; D010375:Pedigree; D011401:Promoter Regions, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha