Does (HFE) hemochromatosis exist            in India?            Rakesh Aggarwal      Department of Gastroenterology      ...
HemochromatosisA progressive increase in body iron content,leading to systemic iron loading of parenchymalcells (particula...
Iron homeostasis in humansPietrangelo. New Engl J Med 2004; 350: 2383-97.
Hemochromatosis: Types• Primary• Secondary  – Parenteral iron overload     • RBCs     • Iron  – Anemias  – Chronic liver d...
HemochromatosisPietrangelo. New Engl J Med 2004; 350: 2383-97.
HFE gene frequency in Caucasians    Population                     Country            Sample   Prevalence of      Allele  ...
C282Y HFE mutation: Indian populationStudy             City          Number of Number of      Number of        % of       ...
HFE C282Y: Indian ThallassemicsStudy             City          Number of Number of      Number of        % of             ...
HFE C282Y: Indian liver disease patientsStudy              City         Number of Number of      Number of        % of    ...
H63D HFE mutation in Indian populationStudy             City         Number of Number of      Number of        % of       ...
HFE H63D: Thallassemia / Liver diseaseStudy               City             Number of Number of      Number of        % of ...
Indian liver disease patients: Fe overloadAuthor      N    FindingsThakur     249   24 (9.6%) had transferrin saturation >...
Indian patients with iron overloadShukla et al. Natl Med J India 2006; 19: 20-3.
Indian patients with iron overloadShukla et al. Natl Med J India 2006; 19: 20-3.
Indian patients with iron overloadShukla et al. Natl Med J India 2006; 19: 20-3.
Indian patients with iron overload                                                 PCR-RFLP for C282YShukla et al. Natl Me...
Indian patients with iron overload     • HFE gene        – None of the 5 patients had C282Y mutation        – One had homo...
Indian patients with iron overload                1                 2              3        4        5                6   ...
Other data from the Indian subcontinent      Family              Origin     Onset    Protein      Exon      AA            ...
Hemochromatosis in India: Summary• Iron overload       Occasional• C282Y mutation      Very infrequent• C282Y HFE disease ...
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Talk: Does hemochromatosis exist in india by Dr. Rakesh Aggarwal

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Talk: Does hemochromatosis exist in india by Dr. Rakesh Aggarwal

  1. 1. Does (HFE) hemochromatosis exist in India? Rakesh Aggarwal Department of Gastroenterology SGPGI, Lucknow
  2. 2. HemochromatosisA progressive increase in body iron content,leading to systemic iron loading of parenchymalcells (particularly hepatocytes) and, eventually,to organ disease.
  3. 3. Iron homeostasis in humansPietrangelo. New Engl J Med 2004; 350: 2383-97.
  4. 4. Hemochromatosis: Types• Primary• Secondary – Parenteral iron overload • RBCs • Iron – Anemias – Chronic liver disease (esp alcohol)
  5. 5. HemochromatosisPietrangelo. New Engl J Med 2004; 350: 2383-97.
  6. 6. HFE gene frequency in Caucasians Population Country Sample Prevalence of Allele sample size C282 frequency homozygotes Electoral roll New Zealand 1,064 1 in 213 6.9% Field survey Australia 3,011 1 in 188 7.3% Primary care USA 4,865 1 in 405 5.0% Health clinic USA 41,038 1 in 270 6.1% Primary care USA/Canada 20,130 1 in 322 5.6%Harrison SA, Bacon BR. J Hepatol 2003; 38: S14-S23.
  7. 7. C282Y HFE mutation: Indian populationStudy City Number of Number of Number of % of subjects Y alleles total alleles Y allellesKaur, 2003 Delhi 116 *1 232 0.4Thakur, 2004 Delhi 134 0 268 0.0Garewal, 2005 Chandigarh 60 0 120 0.0Panigrahi, 2006 Delhi 74 0 148 0.0Dhillon, 2007 Chandigarh 100 0 200 0.0Dhillon, 2007 Chandigarh 80 0 160 0.0Agarwal, 2007 Lucknow 421 0 842 0.0Jain, 2011 Lucknow 502 0 1004 0.0Total 1 2974 0.034* PCR using sequence-specific primers
  8. 8. HFE C282Y: Indian ThallassemicsStudy City Number of Number of Number of % of subjects Y alleles total alleles Y allellesKaur, 2003 Delhi 75 *6 150 4.0Garewal, 2005 Chandigarh 215 0 430 0.0Agarwal, 2006 Lucknow 147 0 294 0.0Agarwal, 2007 Lucknow 308 0 616 0.0Sharma, 2007 Delhi 63 0 126 0.0Total 6 1616 0.371* PCR using sequence-specific primers
  9. 9. HFE C282Y: Indian liver disease patientsStudy City Number of Number of Number of % of subjects Y alleles total alleles Y allellesThakur, 2004 Delhi 249 0 498 0.0Duseja, 2005** Chandigarh 16 0 32 0.0Agarwal, 2006 Lucknow 65 0 130 0.0Panigrahi, 2006*** Delhi 31 0 62 0.0Dhillon, 2007 Chandigarh 236 0 472 0.0Jain, 2011 Lucknow 496 *1 992 0.1Total 1 2186 0.046* PCR-RFLP** Non-alcoholic steatohepatitis*** With transferrin saturation >45%
  10. 10. H63D HFE mutation in Indian populationStudy City Number of Number of Number of % of subjects Y alleles total alleles Y allellesKaur, 2003 Delhi 116 20 232 8.6Panigrahi, 2006 Delhi 74 6 148 4.1Dhillon, 2007 Chandigarh 100 13 200 6.5Dhillon, 2007 Chandigarh 80 6 160 3.8Agarwal, 2007 Lucknow 421 47 842 5.6Jain, 2011 Lucknow 502 46 1004 4.6Total 138 2586 5.3
  11. 11. HFE H63D: Thallassemia / Liver diseaseStudy City Number of Number of Number of % of subjects Y alleles total alleles Y allellesThallassemiaKaur, 2003 Delhi 75 19 150 12.7Agarwal, 2007 Lucknow 308 49 616 8.0Sharma, 2007 Delhi 63 8 126 6.3Total 76 892 8.5Chronic liver diseaseDuseja, 2005 Chandigarh 16 4 32 12.5Panigrahi, 2006 Delhi 31 8 62 12.9Dhillon, 2007 Chandigarh 236 36 472 7.6Jain, 2011 Lucknow 496 60 992 6.0Total 108 1558 6.9
  12. 12. Indian liver disease patients: Fe overloadAuthor N FindingsThakur 249 24 (9.6%) had transferrin saturation >60%Duseja 31 Only 1/23 (5%) had transferrin saturation >45%; Liver biopsy in 16: none had 3+/4+ Perl stainDhillon 236 Only 17 (7.2%) had iron overloadJain 496 Only 13 (2.6%) had iron overload
  13. 13. Indian patients with iron overloadShukla et al. Natl Med J India 2006; 19: 20-3.
  14. 14. Indian patients with iron overloadShukla et al. Natl Med J India 2006; 19: 20-3.
  15. 15. Indian patients with iron overloadShukla et al. Natl Med J India 2006; 19: 20-3.
  16. 16. Indian patients with iron overload PCR-RFLP for C282YShukla et al. Natl Med J India 2006; 19: 20-3.
  17. 17. Indian patients with iron overload • HFE gene – None of the 5 patients had C282Y mutation – One had homozygous H63D mutation – None had previously known splice site mutations – Four had a IVS2+4 T/C change • HAMP gene (Hepcidin) – None had G71A or IVS2+1(-G) mutation • SLC11A3 gene (Ferroportin) – None had G71A or IVS2+1(-G) mutationShukla et al. Natl Med J India 2006; 19: 20-3.
  18. 18. Indian patients with iron overload 1 2 3 4 5 6 1 2 3 4 5 6 Intron Splice Exon site Z92910.1 AAGG GTATGTGGAGAGGGGGC Patient #1 AAGG GTATGTGGAGAGGGGGC Patient #2 AAGG GTACGTCGAGAGGGGGC Patient #3 AAGG GTAYGTGGAGAGGGGGC Patient #4 AAGG GTACGTCGAGAGGGGGC Patient #5 AAGG GTAYGTGGAGAGGGGGC Y = T or CShukla et al. Natl Med J India 2006; 19: 20-3.
  19. 19. Other data from the Indian subcontinent Family Origin Onset Protein Exon AA age change A Bangladesh 19 Hemojuvelin 3 C80Y B Pakistan 26 Hemojuvelin 3 G99R C Pakistan 11 Hemojuvelin 3 G99R D Pakistan 23 Hemojuvelin 3 P192L E Pakistan 32 Hemojuvelin 3 L194P F Sri Lanka 17 Hemojuvelin 4 A343fsX23 G Pakistan 21 Hepcidin 2 R42Sfs H Thailand 38 Ferroportin 7 C326YLok et al. Blood 2009; 114: 20-5.
  20. 20. Hemochromatosis in India: Summary• Iron overload Occasional• C282Y mutation Very infrequent• C282Y HFE disease Extremely rare

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