Celiac disease and HLA-DQ genotype: diagnosis of different genetic risk profiles related to the age in Badajoz, southwestern Spain.

BACKGROUND AND OBJECTIVES: celiac disease is associated with the HLA class II alleles: DQA1*05-DQB1*02 and DQB1*0302. The genetic risk for celiac disease may depend on the presence or absence of such alleles, their combination or number of copies. This study aimed to establish the differences in HLA genotypes between celiac patients diagnosed during childhood and adulthood, and between patients and healthy controls, and to determine the risk of disease in each genotypic category. METHODS: we classified 350 celiac patients at time of diagnosis and 218 controls into 14 categories according to their HLA genotype, based on the presence or absence of risk alleles. RESULTS: we found statistically significant differences between the genotype frequencies of celiac patients diagnosed as being children and adults. DQA1*05 (x 1 copy), DQB1*02 (x 1 copy), DQB1*0302 (x 0 copies) was the most frequent genotype in individuals diagnosed in childhood, whereas DQA1*05 (x 1 copy), DQB1*02 (x 2 copies), DQB1*0302 (x 0 copies) was the most frequent in adults. The risk for disease in each genotypic category in celiac children and adults turned out to be different. The presence of DQB1*0302 did not increase risk in children, but did in adults. CONCLUSION: in our celiac population, we found a different genetic pattern according to age of diagnosis. That could suggest that the pathogenic mechanism of the disease is not exactly the same in both age groups, which could somehow determine clinical presentation of the disease, its epidemiology, coexisting diseases, and complications.

Celiac disease and HLA-DQ genotype: diagnosis of different genetic risk profiles related to the age in Badajoz, southwestern Spain / Enfermedad celiaca y genotipo HLA-DQ: diagnóstico de diferentes perfiles de riesgo genético relacionados con la edad en Badajoz, suroeste de España

Background and objectives: celiac disease is associated with the HLA class II alleles: DQA1*05-DQB1*02 and DQB1*0302. The genetic risk for celiac disease may depend on the presence or absence of such alleles, their combination or number of copies. This study aimed to establish the differences in HLA genotypes between celiac patients diagnosed during childhood and adulthood, and between patients and healthy controls, and to determine the risk of disease in each genotypic category. Methods: we classified 350 celiac patients at time of diagnosis and 218 controls into 14 categories according to their HLA genotype, based on the presence or absence of risk alleles. Results: we found statistically significant differences between the genotype frequencies of celiac patients diagnosed as being children and adults. DQA1*05 (x 1 copy), DQB1*02 (x 1 copy), DQB1*0302 (x 0 copies) was the most frequent genotype in individuals diagnosed in childhood, whereas DQA1*05 (x 1 copy), DQB1*02 (x 2 copies), DQB1*0302 (x 0 copies) was the most frequent in adults. The risk for disease in each genotypic category in celiac children and adults turned out to be different. The presence of DQB1*0302 did not increase risk in children, but did in adults. Conclusion: in our celiac population, we found a different genetic pattern according to age of diagnosis. That could suggest that the pathogenic mechanism of the disease is not exactly the same in both age groups, which could somehow determine clinical presentation of the disease, its epidemiology, coexisting diseases, and complications (AU)

[Hereditary hemochromatosis: phenotypic study in a Spanish population]. / Hemocromatosis hereditaria: estudio fenotípico de una población española.

BACKGROUND AND OBJECTIVE: Hereditary hemochromatosis (HH) displays an important phenotypic variability and is a disease influenced by many factors. PATIENTS AND METHOD: We included 88 patients with HH. Main clinical and laboratory data were analyzed, and the influence of 6 variables on intensity of iron overload was evaluated. RESULTS: In 38.6% (95% confidence interval [CI], 28.5-49.6%) patients, none of the typical symptoms of the disease was observed. 30,9% (95% CI, 21.7-41.7%) showed abnormalities of the glucose metabolism. We detected an increase in sideremia in 75.0% patients (CI 95%, 64.4-83.3%), transferrin saturation index (TSI) in 95.4% (CI 95%, 88.1-98.5%) and ferritin in 93.2% (CI 95%, 85.1-97.1%) of patients. In addition, we observed increased values of GPT and alkaline phosphatase in an appreciable percentage of patients. Ferritin was significantly higher in men (1329.4 [913.2] ng/ml vs 656.6 [644.5] ng/ml; p < 0.001), and in those older than 45 years (1293.9 [1006.9] ng/ml vs 868.9 [642.8] ng/ml; p = 0.023] and in not blood donors (1205.2 [926.8] vs 524.8 [365.9] ng/ml; p < 0.001). TSI was 81.9% (19.6) in C282Y homozygotes and 65.7% (19.2) in the rest of HFE genotypes (p = 0.002). Differences of TSI with regard to sex, age or status of blood donor were not detected. Sideremia was significantly higher in patients infected by virus C (251.8 [24.4] microg/dl vs 182.8 [45.8] microg/dl; p = 0.001). CONCLUSIONS: HH patients have a noticeable phenotypic variability, and for that reason clinical symptoms are only orientative for the diagnosis. The relationship between HH and glucose metabolism should be investigated further. Iron parameters can be influenced by age, sex, HFE genotype, blood donation, alcohol intake and hepatitis C virus infection.

Hemocromatosis hereditaria: estudio fenotípico de una población española / Hereditary hemochromatosis: phenotypic study in a Spanish population

Fundamento y objetivo: La hemocromatosis hereditaria (HH) presenta una importante variabilidad fenotípica y es una enfermedad en la que influyen muchos factores. Pacientes y método: Incluimos a 88 pacientes diagnosticados de HH, en los que se analizó los principales datos clínicos y analíticos y se valoró la influencia de 6 variables en la intensidad de la sobrecarga de hierro. Resultados: Un 38,6% (intervalo de confianza [IC] del 95%, 28,5-49,6) de los pacientes no mostró ninguno de los síntomas típicos de la enfermedad. Un 30,9% (IC del 95%, 21,7-41,7) presentaba alteraciones del metabolismo de la glucosa. Se detectó elevación de la sideremia en un 75,0% (IC del 95%, 64,4-83,3), del índice de saturación de la transferrina (IST) en un 95,4% (IC del 95%, 88,1-98,5) y de la ferritina sérica en un 93,2% (IC del 95%, 85,1-97,1) de los casos, respectivamente, además de objetivarse una elevación de la alaninoaminotransferasa y de la fosfatasa alcalina en un porcentaje apreciable de pacientes. La ferritina se elevó significativamente más en varones (1.329,4 [913,2] frente a 656,6 [644,5] ng/ml; p < 0,001), en mayores de 45 años (1.293,9 [1.006,9] frente a 868,9 [642,8] ng/ml; p = 0,023) y en no donantes de sangre (1205,2 [926,8] frente a 524,8 [365,9] ng/ml; p < 0,001). El IST fue del 81,9 (19,6%) en los homocigotos C282Y y del 65,7 (19,2%) en el resto de genotipos HFE (p = 0,002). No se detectó diferencias del IST respecto al sexo, la edad o la situación de donante de sangre. La sideremia fue significativamente mayor en los infectados por el virus de la hepatitis C (251,8 [24,4] frente a 182,8 [45,8] µg/dl; p = 0,001]). Conclusiones: Los pacientes de HH presentan una marcada variabilidad fenotípica, por lo que los síntomas sirven únicamente como orientación diagnóstica. Debe profundizarse en la relación entre la HH y el metabolismo de la glucosa. Los índices relacionados con el hierro pueden estar influidos por la edad, el sexo, el genotipo, la donación habitual de sangre, la ingesta de alcohol y la infección por el virus de la hepatitis C

Background and objective: Hereditary hemochromatosis (HH) displays an important phenotypic variability and is a disease influenced by many factors. Patients and method: We included 88 patients with HH. Main clinical and laboratory data were analyzed, and the influence of 6 variables on intensity of iron overload was evaluated. Results: In 38.6% (95% confidence interval [CI], 28.5-49.6%) patients, none of the typical symptoms of the disease was observed. 30,9% (95% CI, 21.7-41.7%) showed abnormalities of the glucose metabolism. We detected an increase in sideremia in 75.0% patients (CI 95%, 64.4-83.3%), transferrin saturation index (TSI) in 95.4% (CI 95%, 88.1-98.5%) and ferritin in 93.2% (CI 95%, 85.1-97.1%) of patients. In addition, we observed increased values of GPT and alkaline phosphatase in an appreciable percentage of patients. Ferritin was significantly higher in men (1329.4 [913.2] ng/ml vs 656.6 [644.5] ng/ml; p < 0.001), and in those older than 45 years (1293.9 [1006.9] ng/ml vs 868.9 [642.8] ng/ml; p = 0.023] and in not blood donors (1205.2 [926.8] vs 524.8 [365.9] ng/ml; p < 0.001). TSI was 81.9% (19.6) in C282Y homozygotes and 65.7% (19.2) in the rest of HFE genotypes (p = 0.002). Differences of TSI with regard to sex, age or status of blood donor were not detected. Sideremia was significantly higher in patients infected by virus C (251.8 [24.4] µg/dl vs 182.8 [45.8] µg/dl; p = 0.001). Conclusions: HH patients have a noticeable phenotypic variability, and for that reason clinical symptoms are only orientative for the diagnosis. The relationship between HH and glucose metabolism should be investigated further. Iron parameters can be influenced by age, sex, HFE genotype, blood donation, alcohol intake and hepatitis C virus infection