Frequency of primary iron overload and HFE gene mutations (C282Y, H63D and S65C) in chronic liver disease patients in north India

Abstract

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.

Obscure pathogenesis of primary iron overload in Indians warrants more focused research

“…Neither the patients with heterozygous H63D mutation, nor the lone compound heterozygote individual (C282Y/H63D) had primary iron overload. These observations are in concordance with previous studies from India where C282Y has not been identified except for a single individual from Punjab in northern India, and a more widespread distribution of H63D mutation has been reported [4][5][6][7][8]. The H63D mutation is widely distributed in nearly all populations with a variable allele frequency and haplotype analysis suggests that it has occurred earlier to the C282Y mutation.…”

“…The H63D mutation is widely distributed in nearly all populations with a variable allele frequency and haplotype analysis suggests that it has occurred earlier to the C282Y mutation. Its frequency varies from 9.1% to 13.9% in different studies from India [5][6][7][8] and several studies have showed that even H63D homozygotes have no evidence of iron overload. An independent role of H63D mutation in causing hereditary hemochromatosis is not established yet.…”

Iron Metabolism in Nonalcoholic Fatty Liver Disease

“…Many previous studies conducted in predominantly Caucasian populations suggested that HFE mutations are more common among patients with NASH or NAFLD, compared to control populations, implicating HFE as a susceptibility locus for this disease [3,8,[71][72][73][74]. Not surprisingly, HFE mutations were infrequent among NASH cohorts in the non-Caucasian populations of Brazil [75], Japan [76,77], Taiwan [78] and India [79,80]. However, a recent study suggests that H63D HFE mutations may be more prevalent among Koreans with NAFLD than control subjects [81].…”

The Riddle of Nonalcoholic Fatty Liver Disease: Progression From Nonalcoholic Fatty Liver to Nonalcoholic Steatohepatitis

“…However, H63D heterozygosity was found in 16.9% of Asian Indians with NASH when compared to only 12% in controls, suggesting that primary iron overload in Indians is non HFE type. 54 Although genetic susceptibility has been identified for NAFLD, further research should focus on gene-gene and gene-nutrient interactions employing advanced genomic techniques.…”