Cytokine IL-1 beta but not IL-1 alpha promoter polymorphism is associated with Alzheimer disease in a population from the Canary Islands, Spain.

AIMS: Previous studies have reported the presence of low-grade inflammation in Alzheimer disease (AD). Based on these data, our work attempts to investigate the effects of some promoter polymorphisms of pro-inflammatory cytokines [interleukin (IL)-1 alpha and IL-1 beta] on AD. PATIENTS AND METHODS: A PCR-RFLP technique was used to analyze the promoter polymorphisms of both IL-1 alpha (-889 C/T) and IL-1 beta (-511 C/T) and the APOE genotype from the DNA samples of 282 patients (according to NINCDS-ADRDA criteria) and 312 control subjects. RESULTS: (i) The risk of developing AD in our population was associated with the IL-1 beta (-511 C/T) promoter polymorphism; (ii) such risk was independent of the risk factor allele in the APOE gene (APOE4); and (iii) the IL-1 alpha promoter polymorphism (-889 C/T) was not associated with the disease. CONCLUSION: In our population, IL-1 beta promoter polymorphism (-511 C/T) is an independent risk factor for AD.

[Autoimmune diseases and multiple sclerosis]. / Enfermedades autoinmunes y esclerosis múltiple.

INTRODUCTION: Multiple sclerosis (MS) is a demyelinating disease affecting the central nervous system with an unknown origin, although the immunological system plays a crucial role in its pathogenesis. It has been observed that the relatives of MS patients very often have other autoimmune diseases (ADs) and it has been suggested that there may be susceptibility genes that are common to this group of diseases. AIMS: Our aim was to estimate the prevalence of ADs in first and second degree relatives of patients with MS and to determine the coexistence of other ADs in MS patients. PATIENTS AND METHODS: We selected 251 patients with MS defined by the Poser criteria and face-to-face interviews with the patients and/or their relatives were conducted to investigate the following ADs: MS, rheumatoid arthritis, systemic lupus erythematosus, polyarteritis nodosa, autoimmune thyroid disease (ATD), inflammatory bowel disease, myasthenia gravis, type I diabetes mellitus (DMI) and psoriasis. RESULTS. 29.9% of the patients with MS had a first and/or second degree relative with an AD. Prevalence of ADs in first degree relatives was 15.5%, 30% in familial MS and 40% if the patient had both MS and another AD. The most frequent ADs were: MS 27%, psoriasis 18%, ATD 16% and DMI 15%. 15 patients had MS and another AD: six ATD, three DMI, four psoriasis, one inflammatory bowel disease and one myasthenia gravis. CONCLUSIONS: These findings lend support to the existence of susceptibility genes that are common to the different ADs and would act as risk factors.

[Familial multiple sclerosis in Canary Islands]. / Esclerosis múltiple familiar en Canarias.

INTRODUCTION: Multiple sclerosis (MS) is an autoimmune disease that occurs in genetically predisposed individuals. Its inheritance is polygenic. Genetic epidemiology studies have shown an increased familial aggregation. AIM. To determine the prevalence of familial MS (fMS) in a series of patients from the Canary Islands. PATIENTS AND METHODS: From a cohort of 266 patients with defined MS, during a 6-year period, we investigated prospectively by personal interviews the presence of MS on first and second degree relatives. We analysed as well the presence of HLA DRB1 in affected families, and also clinical and demographic characteristics in fMS and compared them with sporadic MS (sMS). RESULTS: fMS prevalence was 13.9% (27 non-related families with 50 affected individuals). The HLA DRB01*1501 allele were present in 51,8% of familial cases. We could not found either intrafamilial concordance in clinically affected regions and age of onset or clinical evolution. We have not found any phenotypic differences between familial and sMS. CONCLUSIONS: The prevalence of fMS in our series is comparable to that in other Mediterranean populations. Our results do not support that fMS was a different clinical entity of sMS and intrafamilial concordance in its clinical expression.

[Gender has a strong modulating effect on the risk of Alzheimer's disease conferred by the apolipoprotein E gene in the population of the Canary Islands, Spain]. / Fuerte modulacion de genero sobre el riesgo conferido por el gen de la apolipoproteina E para la enfermedad de Alzheimer en la poblacion de las Islas Canarias, España.

OBJECTIVES: Apolipoprotein E (ApoE) gen has been found to confer risk for Alzheimer disease in every population studied. We are interested in analyzed the exonic variants and the promoter polymorphisms in our Canary population. SUBJECTS AND METHODS: By means of PCR RFLP analysis of DNA from patients (NINCS ADRDA criteria) and controls (cognitive state CAMCOG test measured) we analyzed the known exonic and promoter polymorphism of ApoE gen. RESULTS: We have found an association of Alzheimer disease risk based on exonic variants of ApoE gen, with a clear cut dose effect on susceptibility and no risk conferred by the promoter polymorphisms. Age at onset are not affected by variants of ApoE gen, and patients gender strongly modulate the disease susceptibility. CONCLUSION: We have found in our Canary population an association between Alzheimer disease with exonic variants of ApoE gen with a strong modulation by the patients gender.

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.