Biomedical subjects

Miguel Fernandez-Arquero

Publications and source records attributed to Miguel Fernandez-Arquero.

7 recordsLinked to original sources

PubMed2006

Case report of a Spanish patient with arrhythmogenic right ventricular cardiomyopathy and palmoplantar keratoderma without plakoglobin and desmoplakin gene modifications.

We report a case of a 43 year old man from Spain, who has been diagnosed with Naxos disease. It is a hereditary disorder characterized by palmoplantar keratoderma, woolly hair and cardiomyopathy, which has been associated with a mutation in plakoglobin encoding gene in chromosome 17q21. In the patient, the direct sequencing of the plakoglobin gene discarded TG deletion at 2157 characteristic of Naxos disease. Analysis of the reported desmoplakin mutations associated with Carvajal Syndrome, another ARVC disease, that it is also accompanied with a skin and hair disorder, also failed to reveal mutations in desmoplakin gene. These results suggest the existence of other causative genes and/or other putative sites in desmoplakin/plakoglobin encoding genes than those recently published.

Adult↗

PubMed2006

MDR1 gene: susceptibility in Spanish Crohn's disease and ulcerative colitis patients.

BACKGROUND: The multidrug resistance MDR1 gene codes for a membrane transporter associated with inflammatory bowel disease. The polymorphism Ala893Ser/Thr (G2677T/A) previously showed significant association with Crohn's disease (CD) and the Ile1145Ile (C3435T) with ulcerative colitis (UC). We studied the association of both polymorphisms in an independent population to reveal the impact of the MDR1 gene on predisposition to inflammatory bowel disease. METHODS: Case-control study with 321 CD and 330 UC white Spanish patients recruited from the same center, and 352 healthy ethnically matched controls. RESULTS: A significant association of MDR1 C3435T with CD was observed (CC vs (CT + TT): P = 0.007; OR [95% CI] = 1.58 [1.12-2.23]). A CD susceptibility haplotype 2677T/C3435 was identified. No difference between UC patients as a whole and controls could be detected. CONCLUSIONS: New evidence supports the role of the MDR1 gene on CD susceptibility. Therefore, considering our results and those from others, the MDR1 gene behaves as a common risk factor for both CD and UC. We discovered that the C3435 allele conferring susceptibility to CD is different from the described 3435T UC risk allele.

Adult↗

PubMed2005

Interleukin-10 polymorphisms in Spanish patients with IBD.

BACKGROUND: Inflammatory bowel disease (IBD) is considered a heterogeneous, complex polygenic disease where both genetic and environmental factors are involved in the development of the disease. Interleukin-10 (IL-10) is a regulatory cytokine that might play an important role in disease pathogenesis. IL-10 contains single nucleotide polymorphisms and 2 polymorphic microsatellites in the 5'-flanking region. Our aim was to ascertain if any of these polymorphic markers is associated with IBD among Spanish patients. METHODS: We genotyped 470 patients with IBD, 242 with ulcerative colitis and 228 with Crohn's disease (CD), and 572 ethnically matched controls for microsatellites IL-10R and IL-10G and 2 single nucleotide polymorphisms at positions -1082 and -819 in the proximal promoter of the gene. RESULTS: IL-10G14 microsatellite allele as well as -1082G allele were significantly increased in patients with CD. The combined presence of both alleles in 1 individual notably increased the risk to develop CD (P = 0.00006, odds ratio = 3.18). CONCLUSION: IL-10 polymorphisms contribute to susceptibility to CD in Spanish population.

Base Sequence↗

PubMed2004

Association of the major histocompatibility complex with response to infliximab therapy in rheumatoid arthritis patients.

OBJECTIVE: To determine whether major histocompatibility complex (MHC) polymorphisms are associated with a good or poor response to infliximab therapy in patients with rheumatoid arthritis (RA). METHODS: Seventy-eight infliximab-treated patients with RA were genotyped for HLA-DRB1, HLA-DQA1, HLA-DQB1, MHC class I chain-related gene A (MICA) transmembrane polymorphism alleles, and tumor necrosis factor a (TNFa), TNFb, TNFc, TNFd, TNFe, D6S273, HLA-B-associated transcript 2 (BAT2), and D6S2223 microsatellites. Chi-square tests were performed to compare allele proportions between responder and nonresponder patients. A control sample of 342 healthy individuals was also included to detect linkage disequilibrium between pairs of markers. RESULTS: Among responders, the frequency of the TNFa11;b4 minihaplotype was increased (41% versus 16% in nonresponders; P = 0.01) and that of the D6S273_3 allele was decreased (32% versus 56% in nonresponders; P = 0.04). The D6S273_4/BAT2_2 pair was much more frequently observed among responders (46% versus 11% in nonresponders; P = 0.001). When compared with controls, this pair of alleles was found to be associated only with the group of responder patients (46% in responders versus 17% in controls; P = 0.00002). Most of the time, these markers are present in a DRB1*0404/D6S273_4/BAT2_2/TNFa11;b4 context. No statistically significant differences were observed for MICA and D6S2223 polymorphisms and for shared epitope status. CONCLUSION: The data suggest that genetic determinants of response to infliximab therapy exist in the HLA complex.

Adult↗

PubMed2004

IBD1 and IBD3 determine location of Crohn's disease in the Spanish population.

BACKGROUND: Crohn's disease is a heterogeneous disease from both genetic and clinical points of view. AIMS: To look for associations between distinct genetic polymorphisms and clinical subgroups of the disease. SUBJECTS: A total of 210 patients and 343 healthy control subjects, all adult, unrelated, white, Spanish individuals. METHODS: DNA was purified from peripheral blood samples and was typed by sequence-specific oligonucleotide polymerase chain reaction (PCR) method for human leukocyte antigen (HLA)-DRB1 alleles (IBD3) and by allele-specific PCR for NOD2/CARD15 (IBD1) polymorphisms. RESULTS: NOD2/CARD15 mutations and HLA-DRB1*07 confer susceptibility only to the ileal location of the disease, whereas HLA-DRB1*0103 is associated only with the colonic location of the disease. The IBD3 effect was overshadowed by IBD1 mutations when present. CONCLUSION: The studied genetic polymorphisms of Crohn's disease basically determine the location of the disease and, only secondarily, the clinical form of the disease. This appears to be true for both inflammatory bowel diseases as HLA-DRB1*0103 is associated both with colonic Crohn's disease and ulcerative colitis.

Adolescent↗

PubMed2002

MHC susceptibility genes to IgA deficiency are located in different regions on different HLA haplotypes.

Familial predisposition to IgA deficiency (IgAD) suggests that genetic factors influence susceptibility. Most studies support a polygenic inheritance with a susceptibility locus (designated IGAD1) in the MHC, but its exact location is still controversial. This study aimed to map the predisposing IGAD1 locus (or loci) within the MHC by investigating the pattern of association of the disease with several markers in the region. DNA-based techniques were used to type individual alleles of four polymorphic HLA genes (HLA-DR, -DQA1, -DQB1, and HLA-B), six microsatellites (all located between HLA-DR and HLA-B), and three single nucleotide polymorphisms on the TNF gene. The frequencies of these alleles were compared among ethnically matched populations comprising 182 patients and 343 controls. Additionally, we investigated parents and siblings of 100 of these patients. All four parental haplotypes were established in each family (n = 400), and transmission disequilibrium tests were performed. Surprisingly, our results did not support the hypothesis of a unique susceptibility gene being shared by all MHC susceptibility haplotypes. On HLA-DR1 and -DR7-positive haplotypes IGAD1 mapped to the class II region, whereas on haplotypes carrying HLA-DR3 the susceptibility locus mapped to the telomeric end of the class III region, as reported previously. Our results show how, in complex diseases, individuals may be affected for different genetic reasons and a single linkage signal to a region of a chromosome may actually be the result of disease-predisposing alleles in different linked genes in different pedigrees.

Alleles↗

PubMed2002

Interleukin-10 polymorphisms in Spanish multiple sclerosis patients.

Interleukin-10 (IL-10) is an anti-inflammatory cytokine that may be an important regulator in multiple sclerosis (MS) pathogenesis. IL-10 gene contains three single nucleotide polymorphisms (SNPs) and two polymorphic microsatellites in the 5'-flanking region. Our aim was to ascertain if any of these polymorphic markers is associated or linked to MS among Spanish patients. We have genotyped 300 patients and 357 ethnically matched controls for the microsatellites, and most of them also for the promoter SNPs. We included in this study the parents of 63 patients in order to perform a TDT analysis as well. IL-10G12 allele was significantly increased in MS patients (17% versus 11% in controls; p=0.004; p(c)<0.05). No other allele showed a significant difference between patients and controls, and the TDT analysis yielded negative results. The data indicate that IL-10 is not a major susceptibility locus in MS, but in our population it might, however, have a minor role.

Adult↗