C282Y hemochromatosis gene mutation and iron parameters in dialysis patients.

BACKGROUND: Hereditary hemochromatosis is an autosomal recessive condition causing excessive intestinal iron absorption related to C282Y hemochromatosis mutation gene. Dialysis patients receive intravenous iron supplements as treatment for anemia. The gene mutation frequency and its influence on iron deposits and intravenous iron response are unknown in these patients. STUDY DESIGN: Prospective observational. SETTING AND PARTICIPANTS: 290 dialysis patients in Gran Canaria, Spain. OUTCOMES AND MEASUREMENTS: The C282Y hemochromatosis mutation gene was studied. Other active players in iron metabolism have not been included in this study. Red cell parameters, serum iron, transferrin and ferritin concentrations were measured every 2 months for 2 years. RESULTS: No differences in allelic and genotypic frequencies between dialysis patients and the general population were detected. Baseline clinical or analytical parameters were similar in C282Y +/- and C282Y -/- patients. Among those who did not need intravenous iron treatment, C282Y+/- patients maintained constant serum ferritin (302.1 ± 216.7 vs. 319.5 ± 300.5 µg/l after 4 months), whereas C282Y-/- patients showed decreased levels during the same period (306.7 ± 212.2 vs. 221.6 ± 167.8 µg/l, p < 0.001). After 4 months of parenteral iron, serum ferritin increased more intensely in C282Y +/- patients than in C282Y -/- patients (934.2 ± 195.8 vs. 658.7 ± 259.9 µg/l, p < 0.001). A multivariance analysis identified the C282Y allele as the most important factor that explains this difference. CONCLUSIONS: Heterozygosity for the C282Y allele of the hemochromatosis mutation gene could be associated with differences in iron parameters in dialysis patients.

Variabilidad genética en la susceptibilidad y en la gravedad de la neumonía / No disponible

No disponible

Assessment of the DQ heterodimer test in the diagnosis of celiac disease in the Canary Islands (Spain).

BACKGROUND: Celiac disease is a multifactorial disorder of the proximal small intestine associated with a permanent intolerance to gluten. The HLA-DQ(alpha1*0501, beta1*02) heterodimer is strongly associated with this disease. MATERIALS AND METHODS: The authors studied a sample of 354 unrelated Caucasoid individuals: 118 patients with celiac disease and 236 control subjects. All patients and controls subjects were born in Gran Canaria (Canary Islands) at least two generations ago. The authors typed the HLA-DQA1 and DQB1 genes by DNA methods. The positive and negative predictive values of the test were studied. RESULTS: The mean age at diagnosis was 25.4 months, with a statistically significant proportion of females (64.4%, P < 0.002). For DQB1 gene, the susceptibility allele found was DQB1*02 (relative risk [RR] = 7.60, confidence interval [CI]: 5.35-10.78), whereas for the DQA1 gene, the susceptibility alleles found were DQA1*0501 (RR = 2.99, CI: 2.16-4.14) and DQA1*0201 (RR = 1.88, CI: 1.25-2.82). The presence of the DQ(alpha1*0501, beta1*02) heterodimer was strongly associated with the disease (92.4% in the patients group vs. 21.6% in control subjects). HLA-DQ8 heterodimer was absent in the authors' patients. DQB1*02 homozygous subjects presented a higher relative risk for celiac disease. There was no correlation of DQB1*02 dosage with age at onset below 12 years of age or with gender distribution. Sensitivity, specificity, and the positive and negative predictive values of the test were 92.4%, 78.4%, 68.1%, and 95.4%, respectively. CONCLUSIONS: The presence of the DQ2 (DQA1*0501/DQB1*02) heterodimer is strongly associated with celiac disease in the population studied by the authors. The value of this test derives from its ability to exclude disease when a negative result occurs.

Epidemiology of tuberculosis on Gran Canaria: a 4 year population study using traditional and molecular approaches.

BACKGROUND: In recent years several population based studies using restriction fragment length polymorphism (RFLP) analysis have shown a higher rate of recent transmission of tuberculosis than previously thought. This study was undertaken to determine the transmission patterns of tuberculosis and the potential causes of recent transmission on the island of Gran Canaria (Spain). METHODS: The strains of all patients diagnosed with tuberculosis confirmed by culture between 1 January 1993 and 31 December 1996 were typed by RFLP using the insertion sequence IS6110. A cluster was defined as two or more isolates with an identical RFLP pattern. Epidemiological linkage through contact tracing was investigated. RESULTS: Of the total of 719 patients, 153 (21.3%) were excluded because there was inadequate bacterial DNA for genotyping (n=129) or the isolates of Mycobacterium tuberculosis had less than five copies of IS6110 (n=24). The isolates from 409 patients (72.3%) were grouped into 78 different clusters with an estimated 58.5% of the cases being due to recent transmission. Young age was the only significant predictor of clustering. Only in 147 (35.9%) of the 409 patients belonging to a cluster could an epidemiological link be found. 111 patients (19.6%) were identified as having had previous contact with a tuberculosis patient and 81 of them (72.9%) belonged to a cluster. The three largest clusters included 75, 49 and 20 patients, respectively. CONCLUSION: Recent transmission is frequent among patients with tuberculosis on Gran Canaria and could be associated with certain aspects of control measures. Some of the clusters described in the study could be due to the prevalence of particular strains of M tuberculosis on the island.