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

Genes & Immunity volume 3, pages 5–8 (2002)Cite this article

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.

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References

  1. WHO study group report on diabetes mellitus. WHO Technical Report Series 727 1985

  2. Mohan V, Nagalotimath SJ, Yajnik CS, Tripathy BB . Fibrocalculous pancreatic diabetes Diabetes Metab Rev 1998 14: 153–170

    Article  CAS  PubMed  Google Scholar 

  3. Pitchumoni CS . Familial pancreatitis. In: Pai KN, Suman CR, Varghese R (eds) Pancreatic Diabetes Geoprinters: Trivandrum 1970 46–48

    Google Scholar 

  4. Yajnik CS, Sardesai BS, Bhat DS et al. Ketosis resistance in fibrocalculous pancreatic diabetes: II. Hepatic ketogenesis after oral medium-chain triglycerides Metabolism 1997 46: 1–4

    Article  CAS  PubMed  Google Scholar 

  5. Azad Khan AK, Ali L . Tropical calcific pancreatitis and fibrocalculus pancreatic diabetes in Bangladesh J Gastroenterol Hepatol 1997 12: S48–S52

    Article  Google Scholar 

  6. Kambo PK, Hitman GA, Mohan V et al. The genetic predisposition to fibrocalculus pancreatic diabetes Diabetologia 1989 32: 45–51

    Article  CAS  PubMed  Google Scholar 

  7. Mohan V, Chari ST, Hitman GA et al. Familial aggregation in tropical fibrocalculous pancreatic diabetes Pancreas 1989 4: 690–693

    Article  CAS  PubMed  Google Scholar 

  8. Sanjeevi CB, Kanungo A, Shtauvere A, Samal KC, Tripathi BB . Association of HLA class II alleles with different subgroups of diabetes mellitus in eastern India identify different associations with IDDM and malnutrition-related diabetes Tissue Antigens 1999 54: 83–87

    Article  CAS  PubMed  Google Scholar 

  9. Sanjeevi CB, Seshiah V, Moller E, Olerup O . Different genetic backgrounds for malnutrition-related diabetes and type 1 (insulin-dependent) diabetes mellitus in south Indians Diabetologia 1992 35: 283–286

    Article  CAS  PubMed  Google Scholar 

  10. Mohan V, Deepa R, Bhatia E et al. Antibodies to pancreatic islet cell antigens in diabetes seen in southern India with particular reference to fibrocalculous pancreatic diabetes Diabet Med 1998 15: 156–159

    Article  CAS  PubMed  Google Scholar 

  11. Ramachandran A, Snehaltha C, Tuomilehto-Wolf E et al. T1DM in the offspring does not increase the risk of parental T2DM in south Indians Diabetes/Metab Res Rev 1999 15: 328–331

    Article  CAS  Google Scholar 

  12. Price P, Witt C, Allcock R, Sayer D et al. The genetic basis for the association of the 8.1 ancestral haplotype (A1, B8, DR3) with multiple immunopathological diseases Immunol Rev 1999 167: 257–274

    Article  CAS  PubMed  Google Scholar 

  13. Mulcahy B, Waldron-Lynch F, McDermott MF et al. Genetic variability in the tumor necrosis factor-lymphotoxin (TNF-LT) region influences susceptibility to rheumatoid arthritis Am J Hum Genet 1996 59: 676–683

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Hajeer AH, Worthington J, Silman AJ, Ollier WE . Association of tumor necrosis factor microsatellite polymorphisms with HLA-DRB1*04-bearing haplotypes in rheumatoid arthritis patients Arthritis Rheum 1996 39: 1109–1114

    Article  CAS  PubMed  Google Scholar 

  15. De Mouzon A, Docos E, Ohayon E, Hauptmann G . Bf and C4 markers for insulin-dependent diabetes in Basques Lancet 1979 2: 1364

    Article  CAS  PubMed  Google Scholar 

  16. Thomsen M, Molvig J, Zerbib A et al. The susceptibility to insulin-dependent diabetes mellitus is associated with C4 allotypes independently of the association with HLA-DQ alleles in HLA-DR3,4 heterozygotes Immunogenetics 1988 28: 320–327

    Article  CAS  PubMed  Google Scholar 

  17. Nejentsev S, Gombos Z, Laine A-P et al. Non–class II HLA gene associated with type 1 diabetes maps to the 240-kb region near HLA-B Diabetes 2000 49: 2217–2221

    Article  CAS  PubMed  Google Scholar 

  18. Pociot F, Briant L, Jongeneel CV et al. Association of tumur necrosis factor (TNF) and class II major histocompatibility complex alleles with the secretion of TNF-α and TNF-β by human mononuclear cells: a possible link to insulin-dependent diabetes mellitus Eur J Immunol 1993 23: 224–231

    Article  CAS  PubMed  Google Scholar 

  19. Wilson AG, Symons JA, McDowell TL, McDevitt HO, Duff GW . Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation Proc Natl Acad Sci USA 1997 94: 3195–3199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Whichelow CE, Hitman GA, Raafat I, Bottazzo GF, Sachs JA . The effect of TNF*B gene polymorphism on TNF-alpha and -beta secretion levels in patients with insulin-dependent diabetes mellitus and healthy controls Eur J Immunogenet 1996 23: 425–435

    Article  CAS  PubMed  Google Scholar 

  21. Ellegren H . Microsatellite mutations in the germline: implications for evolutionary inference Trends Gene 2000 16: 551–558

    Article  CAS  Google Scholar 

  22. Huxtable SJ, Saker PJ, Haddad L et al. Analysis of parent-offspring trios provides evidence for linkage and association between the insulin gene and type 2 diabetes mediated exclusively through paternally transmitted class III variable number tandem repeat alleles Diabetes 2000 49: 126–130

    Article  CAS  PubMed  Google Scholar 

  23. Udalova IA, Nedospasov SA, Webb GC, Chaplin DD, Turetskaya RL . Highly informative typing of the human TNF locus using six adjacent polymorphic markers Genomics 1993 16: 180–186

    Article  CAS  PubMed  Google Scholar 

  24. Allen MH, Wakelin SH, Holloway D et al. Association of TNFA gene polymorphism at position −308 with susceptibility to irritant contact dermatitis Immunogenetics 2000 51: 201–205

    Article  CAS  PubMed  Google Scholar 

  25. Metcalfe KA, Hitman GA, Fennessy MJ et al. In Finland insulin gene encoded susceptibility to IDDM exerts maximum effect when there is low HLA-DR associated risk Diabetologia 1995 38: 1223–1229

    Article  CAS  PubMed  Google Scholar 

  26. Sham PC, Curtis D . An extended transmission/disequilibrium test (TDT) for multi-allele marker loci Ann Hum Genet 1995 59: 323–336

    Article  CAS  PubMed  Google Scholar 

  27. Risch N, Merikangas K . The future of genetic studies of complex human diseases Science 1996 273: 1516–1517

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We express our thanks to the subjects for participating in the study. We also acknowledge the contribution of the International Program in the Chemical Sciences (IPICS), Uppsala University, Sweden, for awarding Fellowships to Zahid Hassan and Zahangir Md. Chowdhury.

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Author notes

  1. Z Md Chowdhury and M F McDermott: Joint first authorship.

Authors and Affiliations

  1. Bangladesh Institute of Research and Rehabilitation in Diabetes (BIRDEM), Endocrine and Metabolic Disorders, Dhaka, 1000, Bangladesh

    Z Md Chowdhury, Z Hassan & A K Azad Khan

  2. Department of Diabetes and Metabolic Medicine, St Bartholomew’s and The Royal London School of Medicine and Dentistry, Queen Mary’s, University of London, London, UK

    Z Md Chowdhury, M F McDermott, Z Hassan, E Aganna, R A Allotey, B V North, P G Cassell & G A Hitman

  3. Department of Immunopathology, Tissue Typing Unit, Royal London Hospital, Barts and the London NHS Trust, London, UK

    S Davey, P J Sinnott, S K Hemmatpour, S Sherwin & L Ali

Authors
  1. Z Md Chowdhury
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  2. M F McDermott
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  3. S Davey
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  4. Z Hassan
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  5. P J Sinnott
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  6. S K Hemmatpour
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  7. S Sherwin
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  8. L Ali
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  9. E Aganna
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  10. R A Allotey
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  11. B V North
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  12. P G Cassell
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  13. A K Azad Khan
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  14. G A Hitman
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Corresponding author

Correspondence to G A Hitman.

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Chowdhury, Z., McDermott, M., Davey, S. et al. Genetic susceptibility to fibrocalculous pancreatic diabetes in Bangladeshi subjects: a family study. Genes Immun 3, 5–8 (2002). https://doi.org/10.1038/sj.gene.6363814

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  • DOI: https://doi.org/10.1038/sj.gene.6363814

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