HFE, hepcidin and ferroportin gene mutations are not present in Indian patients with primary haemochromatosis.
BACKGROUND
Primary haemochromatosis is characterized by iron overload in the body tissues. It is common in populations of northern European descent. In such populations, 85%-90% of patients with this disease have a C282Y mutation in the HFE gene. In India, the disease is uncommon and the genetic defects associated with it are unknown. We therefore looked for mutations in the HFE and other genes involved in iron metabolism in Indian patients with primary haemochromatosis.


METHODS
Five patients (including a brother-sister pair) with primary haemochromatosis diagnosed on clinical, biochemical and histological findings were studied. Genomic DNA was analysed by sequencing for the presence of mutations in all the 6 exons of the HFE gene and for previously described mutations in genes encoding hepcidin antimicrobial peptide and ferroportin.


RESULTS
No patient had the C282Y mutation. One had homozygous H63D mutation. No other mutation was found in any HFE exon. Two previously reported splice site mutations in the HFE gene (IVS3 + 1 G/T and IVS5+1 G/A) were not detected. Four of the 5 patients had an HFE splice site mutation (IVS2 + 4 T/C; homozygous 2, heterozygous 2); however, this change was as frequent in 29 healthy subjects (homozygous 9, heterozygous 7), and was present in only 1 of the sibling pair patients, indicating that this represented a polymorphism. No patient had any of the previously described mutations in the genes for hepcidin and ferroportin.


CONCLUSIONS
Our patients with primary haemochromatosis lacked mutations in the HFE, hepcidin and ferroportin genes. Further genetic analysis may help identify novel mutations responsible for primary haemochromatosis in these patients.
Shukla
Priyanka
P
Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
Julka
Sandeep
S
Bhatia
Eesh
E
Shah
Sudeep
S
Nagral
Aabha
A
Aggarwal
Rakesh
R
D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000235:genetics*; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000235:genetics*; D005260:Female; D006432:Hemochromatosis / Q000235:genetics*; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D007194:India; D007501:Iron / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D000098742:Ferroportin
D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; C578702:HAMP protein, human; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D000098742:Ferroportin; D007501:Iron