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Celiac disease is insufficiently known in El Salvador. Between July and August 2012, 32 patients (23F, 9M) with ages between 19 and 77 diagnosed with celiac disease, 21 relatives (13F, 8M) of the celiac patients and 8 persons who were in undergoing the diagnostic process were studied. Genomic DNA was extracted from peripheral blood for HLA-DQA1 and HLA-DQB1 genotyping. Polymerase chain reaction-amplified exon 2 amplicons were generated for low-to-medium resolution typing in a combined, single-stranded conformation polymorphism heteroduplex assay by a semi-automated electrophoresis and gel-staining method on the PhastSystem. The biopsy specimens were revised and classified according to a modified Marsh classification of Oberhuber et al. All participants in this study reside in urban areas. Of the 32 cases, 23 were celiac disease risk genotype carriers, with the following distribution: 14 HLA-DQ8 (12F and 2M), 7 HLA-DQ2.5 (3F and 4M), 2 HLA-DQ2.5 and DQ8 (1F,1M). A review was made of clinical history of 9 cases (7F, 2M) who were neither DQ2.5 nor DQ8. Three of them had a Marsh II and 4 Marsh IIIA of the modified histological classification. All patients have responded to a gluten-free diet. Of the seven families studied, the daughter of one patient was found to suffer from celiac disease, one daughter of another patient suffered from Sjogren's syndrome, and the other of rheumatoid arthritis and the sister of another patient has thyroid disease, early menopause and suffered from attacks of migraine. The rest of the first- and second- degree relatives of the seven families have, so far, no clinical evidence of the disease in spite of the fact that 17 have HLA-DQ2.5 and/or DQ8 or DQ9.3/DQ2.2. Therefore, careful follow-up of these individuals is indicated. Eight other subjects mentioned above were not included in the final study because no reliable information could be gathered on their cases. This is the first study using the modified Marsh classification and the full HLA-DQ tying in El Salvador.

Interleukin (IL)-1α, IL-1β, and lL-1ra contribute to regulation of the inflammatory response in periodontal tissues. We aimed to investigate the distribution of polymorphisms in the IL-1 gene family among periodontitis patients and controls, taking into account smoking and microbiology as additional variables. Fifty-three non-smoking and 52 smoking patients with severe adult periodontitis and 53 controls were genotyped for bi-allelic IL-1A-889, IL-1B+3954, and a penta-allelic 86-bp VNTR IL-1RN gene polymorphisms. The presence of Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans was established by culture techniques. We found a higher frequency of allele 2 carriage in IL-1A, IL-1B, and IL-1RN in periodontitis patients who were non-smokers and in whom P. gingivalis and A. actinomycetemcomitans could not be detected (42.1 % vs. 11.3% in controls; P = 0.0068; OR 5.7, 95% CI: 1.6-19.8). Our results provide evidence that polymorphisms in genes of the IL-1 family are associated with severe adult periodontitis in the absence of other risk factors tested in this patient population.

Background: We describe a simple, non-invasive mouthwash sampling method for rapid DNA isolation to detect cytokine gene polymorphisms. In the present paper, interleukin-1 beta (IL-1B) and interleukin-1 receptor antagonist (IL-1RN) gene polymorphisms were studied. Methods: Two mouthwash samples and blood samples were collected from 11 healthy individuals. The second mouthwash sample was stored for 7 days at room temperature. Polymerase chain reaction amplification was used to identify a bi-allelic polymorphism at position +3953 in the IL-1B gene and a variable number of tandem repeats (VNTR) polymorphism in the IL-1RN gene. Results: Our results show that the typing of these cytokine gene polymorphisms using DNA isolated from mouthwash samples did not differ from those obtained by a phenol/chloroform isolation method from EDTA anti-coagulated blood. Moreover, reliable results from mouthwash samples were obtained after storage for at least 7 days at room temperature. Conclusions: Mouthwash can be the method of choice to study gene polymorphisms in periodontitis and other chronic inflammatory diseases.

Susceptibility to multiple sclerosis (MS) is associated with HLA-DRB1 * 1501. Many reports have suggested associations with other loci but these results remain unconfirmed. We studied the IL-1 receptor antagonist (IL-1ra) gene polymorphism and the HLA-DR and DQ allele frequencies by DNA-based methods in both the primary chronic progressive form (PP MS) and the relapsing/remitting form (R/R MS). The frequency of DRB1 * 1501 and IL-1ra allele 2 were significantly higher in R/R MS. Association was more marked in the female sex and in patients with benign forms of R/R MS. On the other hand DR4 subtypes carrying a Val at position 86 in the DR β chain were increased in PP MS. The present study indicates that MS is genetically heterogeneous and shows a combined effect of HLA-DR and IL-1ra genes in susceptibility to the R/R form of the disease.

Interferon-β (IFNβ) therapy is effective in approximately half of the patients with relapsing-remitting multiple sclerosis (RRMS). Clinical non-responders were characterized by an increased expression of IFN response genes before the start of therapy, and a lack of a pharmacologically induced increase in IFN response gene activity. Because Interferon Regulatory Factor 5 (IRF5) is a master regulator of IFN-activity, we carried out a candidate gene study of IRF5 gene variants in relation to the pharmacological and clinical response upon IFNβ treatment. We found that patients with the IRF5 rs2004640-TT and rs47281420-AA genotype exerted a poor pharmacological response to IFNβ compared with patients carrying the respective G-alleles (P=0.0006 and P=0.0023, respectively). Moreover, patients with the rs2004640-TT genotype developed more magnetic resonance imaging (MRI)-based T2 lesions during IFNβ treatment (P=0.003). Accordingly, an association between MRI-based non-responder status and rs2004640-TT genotype was observed (P=0.010). For the rs4728142-AA genotype a trend of an association with more T2 lesions during IFNβ treatment and MRI-based non-responder status was observed (P=0.103 and P=0.154, respectively). The clinical relevance of the rs2004640-TT genotype was validated in an independent cohort wherein a shorter time to first relapse was found (P=0.037). These findings suggest a role for IRF5 gene variation in the pharmacological and clinical outcome of IFNβ therapy that might have relevance as biomarker to predict the response to IFNβ in multiple sclerosis.

Celiac disease (CD) is associated with decreased bone mineral mass. Its pathogenesis is multifactorial since both systemic and local mechanisms may play a role. Our objective was to determine whether single-nucleotide polymorphisms in genes encoding members of the interleukin-1 family are associated with bone damage measured by densitometry in a series of 71 adult CD patients assessed at diagnosis. When compared with non-carrier CD patients, carriers of allele T of the interleukin-1β gene (IL1B-511T) had a significantly lower bone mass at the total skeleton level (p=0.0484) and a greater prevalence of osteopenia/osteoporosis (p=0.0102). To our knowledge, this is the first evidence on the association between a genetic predisposition and low bone mass in CD patients. This finding supports the postulated inflammation-associated bone loss pathogenesis as one of the causes of bone weakness in CD. Fil: Moreno, M.L.. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina Fil: Crusius, J.B.A.. Vrije Universiteit Amsterdam; Países Bajos Fil: Cherñavsky, Alejandra Claudia. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Sugai, E.. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina Fil: Sambuelli, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina Fil: Vazquez, H.. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina Fil: Mauriño, E.. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina Fil: Peña, A.S.. Vrije Universiteit Amsterdam; Países Bajos Fil: Bai, J.C.. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; Argentina

Background: Both multiple sclerosis (MS) susceptibility and MS clinical phenotype are in part genetically determined. αB-Crystallin is a candidate autoantigen in MS, and there are three polymorphisms in the promoter region of the encoding gene ( CRYAB ): at positions −C249G, −C650G, and −A652G. Methods: These polymorphisms were studied in sporadic cases of MS, assessing disease susceptibility, clinical phenotype, and MRI appearance. Results: The CRYAB polymorphisms influenced susceptibility as well as disease expression in MS. Conclusion: Carriers of the rare allele CRYAB –650*C had an increased likelihood of a noninflammatory, neurodegenerative phenotype characterized by a relatively rapid, primary progressive clinical disease course.

Several studies have reported a defective Fas function in patients with multiple sclerosis (MS). We were interested whether this could result from a genetically altered Fas regulation. We examined the FAS 670 polymorphism in 382 patients with MS and 206 controls, and found that the carriership of allele FAS 670*G was significantly less frequent in patients than in controls. We found no association between the carriership of FAS 670*G and clinical features. For a subgroup of patients, longitudinal MRI data were available. We observed similar brain and lesion volumes in carriers and noncarriers of FAS 670*G. These data suggest that FAS 670*G decreases the risk of developing MS, but does not affect the course of disease. D 2002 Elsevier Science B.V. All rights reserved.

AIM: To investigate the association of TNF polymorphisms with chronic atrophic gastritis (CAG) and gastric adenocarcin-oma in Chinese Han patients. METHODS: The TNFa-e 5 microsatellites and 3 RFLP sites were typed using PCR technique, followed by high-voltage denaturing PAGE with silver staining and restriction enzyme digestion respectively in specimens from 53 patients with CAG and 56 patients with gastric adenocarcinoma and 164 healthy controls. The PCR products were cloned and sequenced. RESULTS: The frequency of TNF-β Ncol*1/2 genotype was higher in patients with chronic atrophic gastritis than in healthy controls, but no significant difference was observed (60.38% vs 46.34%, P = 0.076). The frequency of TNa10 allele was significantly higher in patients with chronic atrophic gastritis than in healthy controls (19.81% vs 11.89%, P = 0.04). However, it did not relate to age, gender, atrophic degree or intestinal metaplasia in patients with chronic atrophic gastritis. The frequency of TNF-β Ncol*1/2 and d2/d6 genotypes were significantly higher in patients with gastric adenocarcinoma than in healthy individuals (P > 0.05). However, TNF-β Ncol*1/2 and d2/d6 genotypes did not relate to age, gender, grade of differentiation and clinicopathologic stage in patients with gastric adenocarcinoma. The frequency of TNFa6b5c1 haplotype homozygote was significantly lower in patients with gastric adenocarcinoma than in healthy controls (1.79% vs 15.85%, P = 0.006). CONCLUSION: TNFa10 allele may be a risk factor for chronic atrophic gastritis. TNF-β Ncol*1/2 and d2/d6 genotypes are associated with the susceptibility to gastric adenocarcinoma, whereas TNFa6b5c1 haplotype homozygote may contribute to the resistance against gastric adenocarcinoma.