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C López-Larrea

Publications and source records attributed to C López-Larrea.

At least 19 recordsLinked to original sources
PubMed2006

MHC class I chain-related gene B (MICB) is associated with rheumatoid arthritis susceptibility.

OBJECTIVES: Several recent studies have shown that the MHC class III region, located telomeric to HLA-DRB1, contains an additional genetic factor that predisposes to rheumatoid arthritis (RA). In this study, we investigate whether inhibitor of kappaB-like (IkappaBL), MICB or MICA located in the MHC class III region are the second susceptibility gene associated with RA. METHODS: A total of 154 healthy controls and 140 RA patients were genotyped for HLA-DRB1, MICA, MICB and the polymorphism -62 of the IkappaBL gene. RESULTS: A significant increase of HLA-DRB1 shared epitope (SE) alleles was detected in RA patients (61.4 vs 43.5%, P(c) = 0.01, OR = 2.1, 95% CI = 1.3-3.3). Among SE alleles, the HLA-DRB1*0401 (13.5 vs 5.1%, P(c) = 0.04, OR = 3.2, 95% CI = 1.3-8.1) and HLA-DRB1*0404 (6.4 vs 1.2%, P = 0.02, P(c) = NS) showed the most significantly association with RA. No increase of risk was associated with HLA-DRB1*01. Remarkably, the allele MICB*004 was also significantly associated with RA susceptibility (40.7 vs 23.3%, P(c) = 0.01, OR = 2.2, 95% CI = 1.3-3.7). MICB*004 was in linkage disequilibrium with HLA-DRB1*0404 (lambda(s) = 0.33) and HLA-DRB1*0405 (lambda(s) = 0.34). However, MICB*004 was also increased in HLA-DRB1 SE negative patients (37 vs 21.5%, P = 0.04). No significant association between IkappaBL and MICA with RA was found. CONCLUSIONS: MICB*004 allele was associated with RA susceptibility. This allele was in linkage disequilibrium with HLA-DRB1*0404 and DRB1*0405. The association of MICB with RA susceptibility and the functional role of MIC genes in the pathogenesis of RA converts MICB into a candidate to be an additional MHC gene associated with RA susceptibility.

Adaptor Proteins, Signal Transducing↗
PubMed2005

The HLA-B*5703 allele confers susceptibility to the development of spondylarthropathies in Zambian human immunodeficiency virus-infected patients with slow progression to acquired immunodeficiency syndrome.

OBJECTIVE: To analyze the HLA distribution in a population of individuals from Zambia in order to establish a possible relationship between the progression of human immunodeficiency virus (HIV) infection and the development of spondylarthropathy (SpA). METHODS: A large epidemiologic analysis of rheumatology patients living in Zambia was performed in order to identify those who had SpA. We selected 64 patients with SpA and found that 54 also had HIV type 1 (HIV-1) infection; only 10 were HIV negative. Additionally, we selected 57 HIV-infected individuals without SpA and 43 healthy controls. Among all of the HIV-1-infected patients, 25 SpA-positive and 24 SpA-negative patients were classified as slow progressors to acquired immunodeficiency syndrome (AIDS), and 8 SpA-positive and 26 SpA-negative patients were classified as rapid progressors. All patients were typed for HLA-B alleles. RESULTS: Of the 64 patients with SpA, HIV infection was observed in 54 (84%). The frequency of B*5703 was increased in patients who were SpA positive and HIV positive compared with patients who were SpA negative and HIV positive (P = 0.0002, odds ratio [OR] 8.28). Among patients who were slow progressors to AIDS, this allele was overrepresented in those with SpA compared with those without SpA (corrected P = 0.001, OR 26.25). CONCLUSION: HLA-B*5703 seems to be a protective allele against the progression of HIV infection but could influence the increased incidence of SpA observed in this population.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Interaction between KIR3DL1 and HLA-B*57 supertype alleles influences the progression of HIV-1 infection in a Zambian population.

KIR and HLA loci are both highly polymorphic, and some HLA class 1 products bind and trigger cell-surface receptors specified by KIR genes. We examined whether KIR genes act in concert with HLA-B locus to control HIV-1 infection in a sample of Zambian patients. DNA samples from 88 Zambian patients with HIV-1 were examined. Patients were classified as either slow progressors (SP; n = 54) or rapid progressors (RP; n = 34) to AIDS. All were typed for HLA-B and KIR genes. Our results reveal an association between B*57 supertype (B*57s, which includes B*57 and B*58 alleles) and delayed progression to AIDS (p = 0.0007 by pc = 0.015; OR = 5.25). We also observed an increase incidence of Bw4-I80 in patients with slow progression (p = 0.001 by pc = 0.003, OR = 5). This increase was found to be secondary to B*57s. The presence of both KIR3DL1 and B*57S has a significant effect on progression to AIDS (p = 0.0008; OR = 5.61). B*57s genotypes with another HLA-B allele different from those in the trans position, which also had a specificity different to Bw4-I80 (Bw4-T80 or Bw6), was also greater in the SP than in the RP group (p = 0.00003; OR = 10.11). The presence of the inhibitory allele KIR3DL1 in combination with the HLA-B*57s alleles that contain the Bw4-I80 epitope, has a highly protective effect against progression to AIDS in Zambian patients.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Diverse clinical presentations of celiac disease in the same family.

We performed a family study to evaluate a total of 34 extended family members (8 siblings, 23 children and nephews, and 3 grandchildren) of an adult patient with celiac disease (CD), a 58- year-old male with severe neurologic involvement manifested as myoclonias. We found 3 other members affected with CD (a 44-year old sister, a 39-year old niece, and a 26-year old nephew). Two of them were completely asymptomatic and all had hypertransaminasemia. All exhibited a villous atrophy pattern of the duodenal mucosa (1 mild, 1 moderate, 1 severe). Overall family involvement was 11.8% (4/14). We wish to emphasize the need to perform extended family studies when diagnosing a case of CD, since risk is not restricted to only first-degree relatives.

Adult↗
PubMed2003

Psoriasis vulgaris and psoriatic arthritis share a 100 kb susceptibility region telomeric to HLA-C.

OBJECTIVE: To map the locus for susceptibility to psoriasis in patients with psoriatic arthritis. METHODS: Seventy-four patients with psoriatic arthritis and 95 patients with psoriasis vulgaris were included in this study. Polymorphic genes and microsatellite markers centromeric (C1_2_5) and telomeric (C1_4_4, OTF3, HCR and the corneodesmosin gene) to HLA-C were studied in an association analysis. Typing was also performed on a control population of 104 matched donors. RESULTS: The allele Cw*0602 was associated both with psoriasis [49 vs 21%, Pc<0.0003; odds ratio (OR)=3.6, aetiological factor (AF)=0.72] and with psoriatic arthritis (62 vs 21%, Pc<0.000001; OR=6.1, AF=0.83). In psoriatic patients a susceptibility region telomeric to HLA-C that includes C1_4_4 (56 vs 22%, Pc<0.0002; OR=4.39, AF=0.77), OTF3 (85 vs 60%, Pc<0.0002; OR=3.7, AF=0.73) and HCR (63 vs 26%, Pc<0.00001; OR=3.8, AF=0.74) was observed. In psoriatic arthritis patients the susceptibility region was delimited by HLA-C and C1_4_4 (384 allele, 56 vs 22%, Pc<0.0002; OR=4.37, AF=0.77). CONCLUSIONS: Comparing the susceptibility regions associated with the two diseases, an overlapping interval of 100 kb between HLA-C and OTF3, which might contain the psoriasis gene, can be defined.

Adult↗
PubMed2003

HLA class I variation in the West African Pygmies and their genetic relationship with other African populations.

We have studied the polymorphism of HLA class I in two West African Pygmy populations, namely, the Bakola from Cameroon and the Mbenzele from the Central African Republic. A unique number of HLA alleles and haplotypes showed specific patterns of these populations. In this study, we identify two alleles (B*37, B*41) and three haplotypes (A*30-B*37, A*66-B*41 and A*68-B*58) that appear to be 'private' or typical of Western Pygmies. These data reflect similarities with the AKA Pygmies from the Central African Republic. On the other hand, we failed to identify alleles that are found at high frequencies among other sub-Saharan populations (B*42, B*51). Allelic and haplotypic frequency distributions show differences between the two Pygmy groups, e.g. B*35 was very common in the Mbenzele but has been found to be absent in the Bakola. In contrast, B*53, which is found in the Bakola, has been found to be rare in the Mbenzele Pygmies. In order to analyse the genetic relationships of the Bakola and Mbenzele Pygmies with other sub-Saharan populations, HLA gene frequencies were subjected to the Neighbour-Joining tree analysis. The Mbenzele, Bakola and AKA were found to be relatively close to each other and isolated from other sub-African populations. However, both the genetic distances and the within-group variation suggests that the Bakola are more admixed with Bantu farmers than Mbenzele.

Africa, Western↗
PubMed2003

Cloning and characterization of human complement component C7 promoter.

To study the transcriptional regulation of the human complement component C7, a 1 kb promoter fragment was cloned and the transcription start site was determined. C7 is expressed by the hepatoma-derived cell line Hep-3B, but not by Hep-G2. Transfection of these cell lines with different C7 promoter-luciferase constructs demonstrated that 1 kb of the 5'-flanking region contains the necessary elements for driving C7 transcription in a tissue-specific manner and showed that the sequence between -29/+102 retained the majority of C7 promoter activity in Hep-3B. Electrophoretic mobility shift assays suggested that the binding of the C/EBPalpha transcription factor to a C/EBP sequence located at +42 is essential for C7 expression. To investigate whether the absence of C/EBPalpha expression in Hep-G2 cells is responsible for the lack of C7 transcription, Hep-G2 cells were transfected with a C/EBPalpha expression vector. C/EBPalpha transactivated the C7 luciferase reported gene and restored the C7 expression in Hep-G2 cells.

Base Sequence↗
PubMed2001

Polymorphism in MICA rather than HLA-B/C genes is associated with psoriatic arthritis in the Jewish population.

The aim of this study was to examine whether the association of psoriatic arthritis (PsA) with human leukocyte antigen (HLA) class I genes is secondary to linkage disequilibrium with a nearby gene. We examined a sample of the Jewish population to investigate whether HLA-B/C and DR polymorphism is associated with susceptibility, or whether other closely related class I loci, such as the major histocompatibility complex class I chain-related gene A (MICA) and tumor necrosis factor (TNF), might play a role in disease development. Comparisons of different populations with different HLA profiles would be of value in identifying the candidate genes involved in PSA. Fifty-two patients with PsA and 73 random matched controls from a Jewish population were selected and DNA typed by polymerase chain reaction-single-strand oligonucleotide probe (PCR-SSOP) (HLA-C), PCR sequence-specific primers (PCR-SSP) (HLA-B, -DR), radioactive PCR (MICA-TM polymorphism in the transmembrane region), and PCR-RFLP (TNF). Some findings can be concluded from the study: (1) the frequency of HLA-B*5701, B*3801, B*39, B*27, Cw*0602, Cw*07, DRB1*0402, and DRB1*0701 were not found to be significantly increased in PsA; (2) no significant differences of TNFalpha promoter alleles at positions -308 and -238 were found between PsA and healthy controls; (3) the trinucleotide repeat polymorphism MICA-A9 was present at a higher frequency in PsA patients, (p(c) < 0.009, RR = 3.34, EF = 0.39); and (4) MICA-A9 polymorphism was found in linkage disequilibrium with HLA-B alleles (B*5701, B*3801) described to be associated with PsA in Caucasians. These results suggest that the MICA gene or other nearby gene(s) may be involved in the development of PsA, and it would thus appear that psoriasis vulgaris (PsV) and PsA are associated with different MHC susceptibility genes.

Adult↗
PubMed2001

Genetic variability, molecular evolution, and geographic diversity of HLA-B27.

HLA-B27 represents a family of 23 closely related alleles (B*2701-23) that differ at 24 amino acid positions. The pattern of polymorphisms of B27 was studied, with special reference to synonymous (Ks) and nonsynonymous (Ka) divergence among alleles. B27 alleles are characterized by the enhanced rate of nonsynonymous nucleotide substitution in the peptide-binding region (PBR). The percentage of substitutions between each of the B27 pairs ranges from 0.2%-3% in exons 2-3 to 1.8%-20.1% in the PBR. A phylogenetic analysis of all B27 alleles is described in order to identify subtypes with a common evolutionary history. These results, together with the phylogenetic trees obtained from the comparison between exons 2-3 and PBR indicate that polymorphism of B27 is selectively maintained. Most of the differences are clustered in the C/F pocket affecting the specific binding of antigenic peptides. Gene conversion and point mutation are the most important mechanisms responsible for B27 diversification. The interaction of selection, genetic drift, and recombination events is important for generating polymorphism at B27 alleles. We analyzed a large extended B27 positive population from different parts of the world. Our results indicate that B27 subtypes differ in their ethnic distribution, which may be the result of different genetic and geographical origins. Different factors such as genetic drift, bottleneck effect, and admixture among populations could contribute to the genetic constitution of B27. The striking correlation between the structural features of B27 and the ethnic distribution of these subtypes suggests a model of strong directional evolution, in which the subtypes could have arisen from B*2705.

Africa↗
PubMed2001

New insights regarding HLA-B27 diversity in the Asian population.

A polymerase chain reaction-sequence-specific primer (PCR-SSP) method which distinguishes all B27 alleles described at present (B*2701-23) has been developed. The distribution of B27 alleles was characterised in six different Asian populations. HLA-B*2705, 02, 04, 07, 22 (formerly B*2706) subtypes found in Asian populations differ in their ethnic distribution, which may be the result of different genetic and geographic origins. Furthermore, two novel B27 alleles were found in this study. B*2714 was identified in two Siberians, one of whom was a patient with ankylosing spondylitis. B*2715 was found in two patients with ankylosing spondylitis in Thais. These associations have not previously been reported in either ethnic group.

Alleles↗
PubMed2001

TNF-238A promoter polymorphism contributes to susceptibility to ankylosing spondylitis in HLA-B27 negative patients.

OBJECTIVE: To investigate the relative contribution of MHC loci in their susceptibility to primary ankylosing spondylitis (AS) in HLA-B27 negative patients and to compare the clinical features and genetic factors with those of HLA-B27 positive AS. METHODS: DNA from patients with B27 negative primary AS (n = 28), B27 positive primary AS (n = 77), and matched healthy controls (B27-, n = 100; B27+, n = 70) were analyzed to investigate whether HLA genes determine the disease susceptibility, or whether other closely linked loci might play a role in disease development. HLA typing was carried out by serology and PCR/SSP (HLA-B, -DR), MICA-TM polymorphism in the transmembrane region by radioactive PCR, and tumor necrosis factor-alpha (TNF-alpha) promoter polymorphism at positions -238 and -308 by PCR-RFLP. RESULTS: Subtle clinical differences were found for primary AS, the B27 negative patients being less frequently complicated by acute anterior uveitis and more associated with peripheral arthritis than B27 positive. Differences were found in the distribution of TNF-alpha -238 genotypes among patients with primary AS (B27- vs B27+). The TNF-alpha -238(A) polymorphism was present in 50% of the B27 negative patients carrying the -238 G/A and A/A genotypes and was significantly increased compared with B27 positive AS (odds ratio 4.3) and with the B27 negative control group (OR 5.9). The TNF-alpha genotypes were equally prevalent in B27 positive AS and healthy matched B27 positive controls. No significant HLA and MICA typing differences were found between the populations under study. CONCLUSION: Our results indicate that the polymorphism variation in the TNF-alpha promoter -238.2(A) influences disease susceptibility in B27 negative primary AS but had no effect in our B27 positive AS population.

Adult↗
PubMed2000

HLA-B27 alone rather than B27-related class I haplotypes contributes to ankylosing spondylitis susceptibility.

Characterization of non-B27 susceptibility genes will be required to know the pathogenesis of AS. The aim of this study was to examine whether ankylosing spondylitis (AS) susceptibility is controlled by B27 alone rather than B27 haplotypes and, whether other closely related class I loci, such as MICA and TNFA genes might play a role in AS. Three hundred eleven B27-positive samples from Caucasoid, Asian, and African populations were selected and genotypes were carried out by PCR/SSOP (HLA-B27 and HLA-C), PCR/SSP (MICA-TM polymorphism in the transmembrane region), PCR/SSCP (MICA alleles), and PCR-RFLP (TNF-alpha). Of these, 161 were AS patients, chosen in order to investigate the contribution of TNFA and MICA loci to AS in HLA-B27 positive individuals. Some findings can be concluded from the study: (a) No significant differences of TNF-alpha promoter alleles at position -308 and -238 (A/G) were found between AS patients and B27 matched alleles from healthy controls; (b) strong linkage disequilibrium was found between the B27 and the MICA alleles. The MICA-A4 was found to be in association with B*2705,02,03 and 08; MICA-A5 with B*2704 and B*2707 and MICA-A.5.1 with B*2706; (c) no significant differences of MICA alleles were found between AS and controls carrying the B27-associated alleles, and therefore no evidence is provided for an additional role of MICA gene in AS susceptibility; (d) there are a striking correlations between the structure of B27 extended haplotypes (from MICA region to HLA-C) and the ethnic distribution of these subtypes. The results of differential linkage disequilibrium with HLA-B27 subtypes suggest that B27 itself remains the primary gene for AS susceptibility, and TNFA and MICA are not involved in the pathogenesis of the disease.

Alleles↗
PubMed2000

The OTF3 gene polymorphism confers susceptibility to psoriasis independent of the association of HLA-Cw*0602.

Psoriasis has been strongly associated to HLA-Cw6, but it remains unclear whether Cw6 itself or a closely linked gene is associated with the disease. The aim of this study was to clarify whether the HLA-C itself determines disease susceptibility or whether it acts only as a marker for the susceptibility allele. We examined a sample of 95 type I psoriasis patients and 104 Spanish matched controls to investigate whether HLA-Cw*0602 or other closely related class I loci, such as HLA-B and MICA (which are centromeric to HLA-C), or corneodesmosin gene and octamer transcription factor-3 genes (which are telomeric to HLA-C), might play a part in disease development. DNA samples were genotyped by polymerase chain reaction/sequence-specific primers (HLA-C), polymerase chain reaction/sequence-specific primers (HLA-B), radioactive polymerase chain reaction (MICA-TM polymorphism in the transmembrane region), and polymerase chain reaction/restriction fragment length polymorphism (protein S and octamer transcription factor-3). Our results show a significant increase of Cw*0602 in psoriasis patients (odds ratio = 3.64; pc < 0.0006). A significant association between the beta allele of octamer transcription factor-3 (HindIII) and psoriasis was also detected (odds ratio = 3.76; pc < 0.0003). The allele octamer transcription factor-3B (etiologic fraction = 0.62) was found to be more strongly associated to psoriasis vulgaris than Cw*0602 (etiologic fraction = 0.35) and the increase of octamer transcription factor-3 B allele is independent of the linkage disequilibrium with Cw*0602 as this was also found in Cw*0602 negative patients (odds ratio = 3.63; pc < 0.015, etiologic fraction = 0.55). We did not detect an association between the corneodesmosin gene and psoriasis. This fact suggests that the psoriasis susceptibility gene is located within a critical region of 147 kb, telomeric to HLA-C and centromeric to the corneodesmosin gene, and the association of Cw6 to psoriasis may be secondary to linkage disequilibrium.

Adolescent↗
PubMed1999

The MICA-A9 triplet repeat polymorphism in the transmembrane region confers additional susceptibility to the development of psoriatic arthritis and is independent of the association of Cw*0602 in psoriasis.

OBJECTIVE: To investigate the relative contribution of HLA antigens in the susceptibility to psoriasis and to localize additional genetic factors involved in psoriatic arthritis (PsA). METHODS: DNA from 45 patients with psoriasis, 65 with PsA, and 177 healthy control subjects was examined by polymerase chain reaction (PCR) using sequence-specific oligonucleotide probes to determine HLA-C. To examine whether MICA (class I major histocompatibility complex chain-related gene A) confers additional susceptibility, trinucleotide repeat polymorphism in the transmembrane region of the MICA gene was investigated by radioactive PCR. Further analysis of MICA was made by PCR-single-strand conformational polymorphism to determine the allelic variant corresponding to MICA transmembrane polymorphism. RESULTS: Our results reveal new findings: 1) the frequency of the Cw*0602 allele was significantly increased in both patient groups: psoriasis (corrected P [Pcorr] < 10(-5), relative risk [RR] 6.2), PsA (Pcorr < 10(-6), RR 6.3), 2) the trinucleotide repeat polymorphism MICA-A9 was present at a significantly higher frequency in PsA patients (Pcorr < 0.00035, RR 3.2), whereas a similar distribution was found in both the control and psoriasis population, 3) this polymorphism corresponds to the MICA-002 allele and was found to be overrepresented in patients with the polyarticular form (Pcorr < 0.0008, RR 9.35), 4) the increase in MICA-A9 in PsA patients is independent of linkage disequilibrium with Cw*0602, 5) this allele confers additional relative risk (RR 3.27, etiologic fraction 0.44; etiologic fraction is the proportion of disease cases among the total population that are attributable to 1 allele when the relative risk is > 1) in PsA patients who carry Cw*0602. CONCLUSION: The data obtained in this study are consistent with the polygenic inheritance of psoriasis. Cw*0602 appears to be the stronger genetic susceptibility factor for psoriasis. Independent of the HLA-C association, MICA-A9 polymorphism corresponding to the MICA-002 allele is a possible candidate gene for the development of PsA.

Adult↗
PubMed1999

Susceptibility to ankylosing spondylitis is independent of the Bw4 and Bw6 epitopes of HLA-B27 alleles.

We have characterized HLA-B27 alleles in a sample of the population from the Azores (n=46) with the aim of investigating the contribution of different subtypes to ankylosing spondylitis (AS). The study was carried out using PCR-SSOP and in some samples genomic sequencing was conducted. Some significant new finding have arisen from this study. First, B*2705,B*2702,B*2703,B*2707 and B*2708 alleles were found to be represented in this population. The polymorphism of B27 alleles found in a sample of the population from the Azores is higher than the Caucasian groups described. B*2703 and B*2707 have not previously been described to be represented in Caucasians and this could indicate admixtures with different populations of the world. In addition, the B*2708 allele was found to be associated with AS in a large family from the Azores. This association has not been previously reported in either ethnic group and needs to be confirmed in other population studies. This is of considerable interest since has only been described as a rare subtype underrepresented in the British population and has not been previously found to be associated with AS. B*2708 carries the sequence specifying the Bw6 epitope in contrast to most B27 alleles which carry a Bw4 sequence. Differences in this region (residues 77-83) can alter the F-pocket and affect T-cell recognition. The importance that these molecular changes can play in the pathogenesis of AS is discussed.

Azores↗
PubMed1999

Immunogenetics, HLA-B27 and spondyloarthropathies.

HLA-B27 is the strongest HLA molecule associated with a disease. However, the reason only a small fraction of HLA-B27 positive individuals develop spondyloarthropathies is still unknown. Recent advances in genetics support the fact that additional genetic factors influence the disease and that the environmental factors may be ubiquitous. The mechanism of association of HLA-B27 and disease remains unknown, but recent studies reveal some peculiar properties of accessory molecules in antigen presentation of B27. Furthermore, research has focused on the analysis of HLA-B27-restricted processing and presentation of a bacteria-derived peptide as playing a key role in the development of spondyloarthropathy. Other studies support a more complex interaction between bacteria and HLA-B27 and suggest that other roles unrelated to antigen presentation might contribute to the development of SpA.

Animals↗