[Analysis of the HFE gene in a large Spanish kindred with hereditary hemochromatosis]. / Estudio del gen HFE en una familia española con hemocromatosis hereditaria.

BACKGROUND: Hereditary hemochromatosis (HH) is an inborn error of iron metabolism that is inherited as an autosomal recessive trait. Recently, it has been shown that the HFE gene, located telomeric to HLA-A on chromosome 6 is mutated in most patients with HH. Moreover, the phenotypic expression of hereditary hemochromatosis is influenced by sex and environmental agents such as alcohol and dietary iron intake. SUBJECTS AND METHOD: We have studied 40 subjects from a family some of which members have HH. DNA was obtained from nucleated peripheral blood cells, and exons 2 and 4 and intron 5 of the HFE gene were amplified by PCR and digested with specific restriction enzymes. RESULTS: Analysis of the HFE gene revealed that 29 members of the family carry some of the three HFE mutations (C282Y, H63D and S65C). Nevertheless, only those homozygous for the C282Y mutation develop HH. In this family, the allele 187G of exon 2 mutation is cosegregated with the allele IVS5-47 A in intron 5. CONCLUSIONS: Analysis of the HFE gene in the members of a large Spanish kindred, living in the same geographical area, shows that only those homozygous for the C282Y mutation develop hemochromatosis.

Serum zinc, copper, insulin and lipids in Alzheimer's disease epsilon 4 apolipoprotein E allele carriers.

BACKGROUND: Copper (Cu) and zinc (Zn) have been implicated in the development of Alzheimer's disease (AD) and, in this regard, Cu and Zn serum concentrations have been analysed but with inconclusive results. Serum insulin, glucose and cholesterol concentrations have been related to the apolipoprotein E genotype in non-AD populations. DESIGN: In this study, we have analysed the relationship between serum Cu, Zn, insulin, glucose and lipid parameters (cholesterol, triglycerides, apoA and apoB apolipoproteins) in AD and AD epsilon 4 apolipoprotein E carriers by multivariate analysis using logistic regression, including the variables that showed a significance of P < 0.05 in the bivariate analysis. RESULTS: The results obtained show that epsilon 4 apoE allele is an independent AD risk factor (OR = 6. 67, 95% CI = 2.59-17.16). In AD epsilon 4 apoE allele carriers, we found significantly higher Zn, Cu and insulin serum concentrations. Non-demented control subjects with at least one epsilon 4 apoE allele had the lowest serum insulin concentrations. There was no significant association between epsilon 4 apolipoprotein E allele and lipid parameters in the sample studied. CONCLUSIONS: In AD we have found a significant association between higher serum Zn, Cu and insulin concentrations and the presence of an epsilon 4 apoE allele, but only greater serum Zn concentration appears to be an independent risk factor associated with the development of AD.

Antiphosphatidylserine antibodies in patients with autoimmune diseases and HIV-infected patients: effects of Tween 20 and relationship with antibodies to beta2-glycoprotein I.

Antiphospholipid antibodies (aPL) react with negatively charged phospholipids, which may often be complexed with a protein cofactor such as beta2 glycoprotein (beta2GPI) and prothrombin. Cofactor requirements may be assessed by measuring antibodies to beta2GPI or by adding Tween 20 to some reagents in the assays for aPL (anticardiolipin and antiphosphatidyIserine). We have measured anticardiolipin antibodies (aCL), antiphosphatidylserine antibodies (aPS), and anti beta2 glycoprotein antibodies (abeta2GPI) in the serum of 10 normal subjects, 20 patients with systemic autoimmune diseases (SAD) diagnosed as having systemic lupus erythematosus (SLE) or antiphospholipid syndrome (APS), and 12 patients with HIV infection. Adding Tween 20 to aPS, the assay couldn't differentiate protein cofactor dependent from independent antibodies, but this can be done by measuring abeta2GPI (P= 0.0008). There was a significant correlation between aCL and a(beta)2GPI in the control group and in the patients with SAD, but not in the HIV-positive (HIV+) patients. After excluding the HIV+ patients, the best Spearman correlation was obtained between a(beta)2GPI and aCL (0.64, P< 0.0005). In 3 out of 7 patients with positive a(beta)2GPI and in 5 out of 6 patients with moderate or high positive aCL of the group of SAD, there was a history of venous thrombosis. The presence of moderate or high values of aCL either alone or together with a(beta)2GPI was significantly associated with a history of venous thrombosis (P < 0.05). Moderate or high aCL concentrations and their association with a(beta)2GPI seems to be useful for the assessment of the risk of venous thrombosis in unselected patients with SLE or APS.