HFE Genotypes in Controls and Patients with Primary Haemochromatosis and other Chronic Liver Diseases

¹Barjinderjit kaur Dhillon, ¹Reena Das, ¹G Garewal, ²Y Chawla, ³GR Chandak, ²RK Dhiman
¹Postgraduate Institute of Medical Education and Research, Dept. of Haematology, PGIMER, Sec-12, Chandigarh, India, ²Postgraduate Institute of Medical Education and Research, Dept. of Hepatology, PGIMER, Sec-12, Chandigarh, India, ³Center of Cellular and Molecular Biology, CCMB, habsiguda, Hyderabad, India

Hereditary haemochromatosis is a genetic disorder that results from the disruption of the mechanism that regulates iron absorption. It is commonly encountered in northern European populations and is due to C282Y mutation of HFE gene (85-90%). This disorder is uncommon in India. We attempted to determine the prevalence of iron overload and HFE genotypes in normal as well as Chronic liver disease (CLD) patients. Hundred normal controls and 236 patients of CLD (59; non- alcoholic steatoheptitis, 22; Alcoholic liver disease, 19; viral cirrhosis and 136; cryptogenic cirrhosis) were analysed for iron parameters and DNA analysis for three HFE mutations (C282Y, H63D, and S65C) by PCR- RFLP method was done. Sequencing of the HFE gene in all the cases of primary iron overload was performed. Seventeen primary iron overloaded cases were identified. No patient or individual showed C282Y/S65C mutations. The prevalence of H63D heterozygosity was 11% in normal individuals, 14.4% in 236 patients and 3 out of seventeen showing heterozygosity for H63D (which was not statistically significant). One patient and one normal individual who were homozygous for H63D did not show iron overload. Sequencing revealed one patient with compound heterozygosity for H63D and T218I. Other patients showed normal HFE gene sequence. Seven patients of iron overload showed HFE splice site mutation (IVS2+4T/C; 2 homozygous, 5 heterozygous); however, this change was as frequent in 100 healthy subjects (13 homozygous, 43 heterozygous 43), indicating that this represented a polymorphism. This study confirms that the iron overload in Indian patients of HH is non-HFE type, which is different from Europeans.