Frequency Of The Hemochromatosis Gene (HFE) And Serum Iron Indices In The Henan Population With The Han Nationality In China

Background Hereditary hemochromatosis, caused by the mutations of HFE gene, is an autosomal recessive disease characterized by iron accumulation in the tissue of several organs including the liver, heart, pancreas, pituitary and joints. Abnormal iron absoiption from the small intestine may result in a wide range of common conditions such as arthritis, diabetes, myocardial infarction, stroke and cancer. Early detection is desirable because periodic phlebotomy provides an effective treatment for iron overload and may prevent complications associated with HH. It principally affects populations of Northern European origin or descent. One of two common missense mutations in the HFE gene (C282Y and H63D) is responsible for most cases of hereditary hemochromatosis (HH). The C282Y mutation results in the substitution of tyrosine for cysteine at amino acid position 282 due to the substitution of adenosine for guanosine at nucleic acid position 845 (845G→A). The H63D mutation results in the substitution of aspartate for histidine at amino acid position 63 due to the substitution of guanosine for cytidine at nucleic position 187 (187C→G). The C282Y mutation is detected in 83-100% of HH patients and known to be an excellent marker for HH.The frequencies of C282Y and H63D mutations of the HFE gene associated with hereditary hemochromatosis vary from different populations. The frequency of the C282Y mutation in Caucasians is reported as 5.7% and that of the H63D mutation as 14.0%. In Asian ethnic groups the C282Y mutation was not found and the prevalence of the H63D mutation was 2.2%.It has no reports about the mutation frequency of C282Y and H63D in China mainland so far.ObjectiveOne aim of this study was to investigate the prevalence in the Henan population with the Han nationality in China of the C282Y and H63D mutation in the HFE gene associated with hereditary hemochromatosis. Another aim of this study was to determine whether the C282Y and /or H63D hemochromatosis gene (HFE) is associated with iron overload.SubjectsThe investigation took place in Henan province, one central regions of China. 518 unrelated blood donors with the Han nationality (293 males and 225 females, aged 18～78years, mean age, 29.30±9. 74 years) were recruited for this study. Those with conditions that could increase transferrin saturation (TS) pre-analytically and individuals with abnormal mean corpuscular volume (MCV), low hemoglobin (Hb) and hematocrit (Hct), and high aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values were excluded. All participants were free of the clinical, biochemical, and hematological manifestations of cardiovascular, hepatic, renal, and endocrine disorders.MethodsPolymerase chain reaction (PCR) and restriction enzyme digestion were performed to screen for C282Y and H63D mutations of the HFE on 518 blood samples from healthy volunteer blood donors provided by the Blood Center of Henan Province, and the same blood samples were tested for transferrin saturation (TS) and serum ferritin (SF) .ResultsResults indicate that the C282Y mutation may be rare and absent in the Henan population with the Han nationality in China. Only 2.1% of our population carries one H63D heterozygous mutation, while 0% has C282Y mutation.Iron was divided by the total iron binding capacity and multiplied by 100 to calculate the percentage saturation (transferring saturation). The mean value (±SD) of TS tested was 41.7±15.4% and The mean value (±SD) of SF tested was 116±53 ng/ml。The mean value (±SD) of TS and SF tested was 40.1±15.7%, 102±46ng/ml respectively in H63D heterozygous mutation group. The mean value (±SD) of TS and SF tested was 43.9±15.5%, 119±53ng/ml respectively in normal group.Conclusions1. The frequency of C282Y homozygosity, the potential severity of the disease, the noninvasive approach for diagnosing the disease, and the efficacy and simplicity of treatment constitute a solid rational basis for proposing general screening of the patients with considering the diagnosis of hereditary hemochromatosis.2. There is significant difference between the healthy adult Chinese in Henan province and Caucasian population in USA. The variety of HFE gene mutation frequency is probably one reason, which caused HH incidence of Chinese less than the Caucasian population in Europe and North Amerca.3. This study revealed the absence or rarity of C282Y mutation in our. Although the frequency H63D heterozygosity seems to be higher, the mean TS and SF levels were no significantly higher in individuals with the H63D heterozygous mutation than in normal cases.4. The mean TS and SF in this study was higher than that of Caucasians population.