Frequency of primary iron overload and HFE gene mutations (C282Y, H63D and S65C) in chronic liver disease patients in north India.
OBJECTIVE
To identify the frequency of iron overload and study the three mutations in the HFE gene (C282Y, H63D, and S65C) in patients with chronic liver disorders (CLD) and controls.


METHODS
To identify patients with iron overload (transferrin saturation > 45% in females and > 50% in males and serum ferritin > 1000 ng/mL) we evaluated 236 patients with CLD, including 59 with non-alcoholic steatohepatitis (NASH), 22 with alcoholic liver disease (ALD), 19 of cirrhosis due to viruses (HBV, HCV), and 136 with cryptogenic cirrhosis. Mutations of the HFE gene were analyzed by PCR-RE. hundred controls were screened for iron status and the mutations.


RESULTS
Seventeen patients with CLD showed evidence of iron overload. Fifteen cases of iron overload had cryptogenic cirrhosis and two had ALD. None of the controls showed iron overload. We did not find any individual with 282Y or 65C either in the cases or in the controls. The prevalence of H63D heterozygosity was 12% in normal individuals, 14.8% in 236 patients (16.9% in NASH, 13.6% in ALD, 26.3% in viral and 12.5% in cryptogenic cirrhosis) and the overall prevalence was 13.98%. Only two of the 17 patients with primary iron overload were heterozygous for H63D. One patient with NASH and one normal individual who were homozygous for H63D showed no iron overload.


CONCLUSIONS
Primary iron overload in Indians is non-HFE type, which is different from that in Europeans and further molecular studies are required to determine the defect in various iron regulatory genes.
Dhillon
Barjinderjit Kaur
BK
Department of Haematology, Postgraduate Institute of Medical Education & Research, Chandigarh 160012, India.
Das
Reena
R
Garewal
Gurjeewan
G
Chawla
Yogesh
Y
Dhiman
R K
RK
Das
Ashim
A
Duseja
Ajay
A
Chandak
G R
GR
D000368:Aged; D016022:Case-Control Studies; D002908:Chronic Disease; D004252:DNA Mutational Analysis; D005234:Fatty Liver / Q000150:complications* / Q000208:ethnology / Q000235:genetics; D005260:Female; D000071020:Hemochromatosis Protein; D006579:Heterozygote; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000502:physiology; D006720:Homozygote; D006801:Humans; D007194:India / Q000453:epidemiology; D019190:Iron Overload / Q000150:complications / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics*; D008103:Liver Cirrhosis / Q000150:complications* / Q000208:ethnology / Q000235:genetics; D008108:Liver Diseases, Alcoholic / Q000150:complications* / Q000208:ethnology / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D008875:Middle Aged; D011110:Polymorphism, Genetic; D015995:Prevalence; D011446:Prospective Studies; D044465:White People / Q000208:ethnology / Q000235:genetics
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins