Associations Of Plasma Ferritin,Polymorphism Of Key Genes In Iron Metabolism And Interaction Between Them With Coronary Heart Disease

Although iron plays an important role in cell growth and division, an excess of iron can increase production of free radicals and cause tissue damage, which might participate in the etiology and progression of cardiovascular disease. Many phathology and animal studies have demonstrated this relationship, but some epidemiological studies yielded contradicting results. This might be due to the different population, different study design, and different sample size. We conducted a case-control study which composed of 1,334 case patients and 1,334 age- and sex- frequency matched controls to explore the associations between plasma ferritin levels, polymorphisms of key genes in iron metabolism and CHD.We used ELISA to detect the plasma ferritin levels and PCR to determine the genotypes of genes. And Logistic regression model was used to evaluated the associations between genotypes, plasma ferritin levels and CHD. Background-- The association between body iron stores and coronary heart disease (CHD) was inconsistent. We sought to explore this association in Chinese Han population and further examine the association of the variations in hemochromatosis(HFE) gene and CHD risk.Methods-- We conducted a case-control study including 1,334 CHD patients and 1,334 age- and sex- frequency matched controls. The plasma ferritin levels were measured by enzyme linked immunosorbent assay. Genotypes of the tagging single nucleotide polymorphisms (tagSNPs) were determined by TaqMan SNP allelic discrimination.Results-- The plasma ferritin levels in CHD cases (197.9 ug/L [2.7 to 932.9 ug/L]) were higher than those in controls (179.9 ug/L [21.1 to 878.2 ug/L]; P=0.028). The odds ratios (ORs) across the tertiles of plasma ferritin levels were 1.0 (reference),0.93 (0.76-1.13), and 1.23 (1.02-1.48; P for trend=0.028). Adjustment for the traditional risk factors attenuated the associations to null (P for trend=0.22). Compared with the TT genotype of tagSNP rs9366637, subjects with C allele had higher risk of CHD (OR=1.35 for TC and 1.76 for CC;P=0.001 and<0.001 respectively). After adjustment for the conventional risk factors the results remained unchanged. We did not find significantly different plasma ferritin levels and Hepcidin levels among different genotypes of rs9366637 (P=0.52).Conclusions--The plasma ferritin levels were not significantly associated with CHD risk. However, the SNP rs9366637 in HFE gene was associated with higher CHD risk in Chinese Han population, and there were not significantly different plasma ferritin levels and Hepcidin levels among different genotypes of rs9366637. The underlie mechanism remained to be elucidated in further studies. Background--TFR2 is a homologue of the type transferring receptor 1 (TFR1), it may participate in cellular iron overload. We sought to reveal the associations of plasma ferritin, polymorphisms of TFR2 and CHD in Chinese Han population.Methods--We recruited 1,334 CHD patients and 1,334 age- and sex- frequency matched controls to perform a case-control study. The plasma ferritin levels and Hepcidin levels were measured by ELISA. TaqMan SNP allelic discrimination was used to examine genotypes of the tagSNPs of TFR2.Results-- We did not find any significant association between genotypes of TFR2 (including rs2075674 and rs7385804) and the risk of CHD (OR=1.04(0.86-1.25) for CT; OR=0.78(0.49-1.25) for TT of rs2075674 and OR=0.94(0.79-1.12) for AC; OR=1.15 (0.87-1.52) for CC of rs7385804, respectively). After adjustment for the conventional risk factors of CHD such as smoking, age, gender, history of hypertension and family history of CHD, the results did not alter. And we also did not find significantly different plasma ferritin levels and Hepcidin levels among different genotypes of rs2075674 and rs7385804 (P>0.05).Conclusions-- The SNPs rs2075674 and rs7385804 in TFR2 gene were not associated with higher CHD risk in Chinese Han population and there were not significantly different plasma ferritin levels and Hepcidin levels among different genotypes of rs2075674 and rs7385804. The mechanism remained to be explored in further studies. Objective:To explore the gene-gene interaction of HFE and TFR2 on CHD.Method:We used unconditional Logistic regression model and likehood test to evaluate the gene-gene interaction of HFE and TFR2.Results:We found there were not interactions between the SNPs of HFE and TFR2, after adjustment for the conventional risk factors such as smoking, drinking, age, gender and family history of CHD, the results did not change, we did not find any significant associations between gene-gene interaction of HFE and TFR2 and CHD (P>0.05).Conclusion:There were not significant associations between gene-gene interaction of HFE and TFR2 and CHD.