RESUMEN
We have previously presented evidence that the polymorphism of the FCGR3A gene, encoding the receptor for Fc fragment of immunoglobulin G IIIa (FcγRIIIa) plays a role in the enhancement of circulating immune complexes (CIs) with the occurrence of Mycobacterium tuberculosis heat shock proteins in patients with sarcoidosis (SA). The immunocomplexemia might be caused by decreased affinity of CIs to Fcγ receptors, with the subsequently decreased receptor clearance by immune cells. In the present study we examined whether the polymorphisms of other related genes (FCGR2A, FCGR2C, FCGR3B) encoding other activatory Fcγ receptors, could have a similar effect. To this end, we genotyped 124 patients with sarcoidosis and 148 healthy volunteers using polymerase chain reaction with sequence-specific primers. We revealed a significant decrease in the percentage of the FCGR2A and FCGR2C variants that ensure effective CIs clearance, with a concomitant increase of less functional variants of these genes in Stages I/II, compared with Stages III/IV of SA. There was no aberration in FCGR3B allele/genotype frequencies. We conclude that the FCGR2A and FCGR2C polymorphisms may also contribute to immunocomplexemia present in SA. The assessment of FCGR genes could become a tool in presaging a clinical course of sarcoidosis and in its personalized therapy.
Asunto(s)
Receptores de IgG/genética , Sarcoidosis/genética , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Proteínas Ligadas a GPI/genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
According to the Hutterite chronicles, the Habans arrived from Austrian Tyrol, Switzerland, and northernmost Italy and stayed in four regions of Slovakia (Sobotiste, Vel'ké Leváre, Moravský Svätý Ján, Trencín). There are some communities in western Slovakia that retained their Haban cultural identity and still identify themselves as descendents of the Hutterite population with their own specific customs. Slovak Habans are typical founder population with significant social isolation for which high degree of inbreeding is typical. Present study investigated STR polymorphisms as a powerful genetic tool for population genetic studies. The aim was to perform a comparative, population genetic study based on 15 STR loci widely used in forensic genetics, of the Haban population, the Slovak majority population and the population of Tyrol. We analyzed allele frequencies and other statistical parameters in three selected populations in order to identify groups of specific ethnic origin and establish their genetic relationship. The data set included 110 unrelated Habans and 201 unrelated individuals from the Slovak majority population, as well as allelic frequencies for the population of Austrian Tyrol available in the literature. Population pairwise FST values used as a short term genetic distance between populations showed significant differentiation between the Habans and both reference populations (FST=0.0025 and 0.0042 for comparison with the Slovaks and Austrians, respectively; p<10(-3)). The Slovak Hutterites were demonstrated to be genetically distinct and more closely related to their geographic neighbors than to their historical ancestral population, which may be at least partially explained by gene flow between neighboring Haban and Slovak populations.
Asunto(s)
Cultura , Etnicidad/historia , Filogeografía/historia , Bases de Datos Genéticas , Flujo Génico , Frecuencia de los Genes , Genética de Población , Historia Antigua , Humanos , Italia , Repeticiones de Microsatélite , Polimorfismo Genético , Grupos de Población , Eslovaquia , Estadística como Asunto , SuizaRESUMEN
BACKGROUND: The human leucocyte antigen (HLA) C allele Cw*06 is currently recognized as a major disease allele at the PSORS1 locus. It has been suggested that characterization of this gene could be used as a convenient criterion for classification of psoriasis phenotypes. AIM: To design and optimize a DNA typing procedure, suitable for identification of HLA-Cw*06 and its zygosity status verification in large-scale analyses, and to test for its robustness in a case-control study. METHODS: PCR assays with sequence-specific primers (PCR-SSP) were used for specific detection of HLA-Cw*06. PCR with analysis of restriction fragment length polymorphism was used to distinguish between patients homozygous and heterozygous for HLA-Cw*06. Additionally, those homozygous for HLA-Cw*06 were screened for nonspecific digestion by degenerated PCR-SSP. This three-step procedure was used in the examination of 383 patients with psoriasis that developed at the age of >or= 30 years of age and of 143 healthy subjects from northern Poland. RESULTS: A simple and rapid procedure for screening of HLA-Cw*06 was produced. A significant difference in HLA-Cw*06 frequency between patients with psoriasis and controls was seen (P = 0.02). Detailed examination of the age of disease onset among patients with psoriasis revealed that involvement of HLA-Cw*06 in the genetic background of psoriasis developing as late as the age of 45 years cannot be neglected. CONCLUSIONS: The low cost, high-throughput capacity and requirement for small sample amounts make this procedure a useful one for HLA-Cw*06 typing in clinical practice and large population studies. We recommend that patients with psoriasis diagnosed before 45 years of age should be considered for diagnostic HLA-Cw*06 typing.
Asunto(s)
Antígenos HLA-C/genética , Psoriasis/genética , Adulto , Edad de Inicio , Anciano , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Pruebas Genéticas/métodos , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa/métodosRESUMEN
BACKGROUND: Tumour necrosis factor (TNF)-alpha is considered to be an important mediator in the pathogenesis of psoriasis. Increased levels and activity of this cytokine have been observed in blood and skin of patients with psoriasis. As certain allelic variants of the TNF-alpha gene are associated with increased or decreased production of TNF-alpha, the disturbed cytokine balance may be under genetic control. OBJECTIVES: To investigate the potential association of TNF-alpha promoter alleles within subtypes of psoriasis compared with healthy controls in a northern Polish population. METHODS: We analysed 166 patients with psoriasis vulgaris (134 with type I and 32 with type II) and 65 healthy controls. The polymorphisms -238G/A and -308G/A in the promoter region of the TNF-alpha gene were typed using the amplification refractory mutation system-polymerase chain reaction method. RESULTS: We found that the TNF-alpha-308A allele frequency was significantly decreased among patients with early-onset psoriasis in comparison with control subjects (7.5% vs. 15.4%, P = 0.022), whereas in the same patients the frequency of the TNF-alpha-238A allele was significantly increased as compared with the controls (16.8% vs. 3.1%, P = 0.000017, odds ratio 8.79, 95% confidence interval 2.606-29.678). Patients with early-onset psoriasis with -238 genotype GA or AA were found more often among those with age at onset < 25 years in comparison with those with genotype GG (31.7% vs. 9.1%, P = 0.0312). We also found that the mean +/- SD age at onset among -238A carriers was significantly lower in comparison with that associated with the -238GG genotype (13.5 +/- 7.4 vs. 19.2 +/- 9.9 years, P = 0.0132). CONCLUSIONS: Our study confirming the association between -238 G/A TNF-alpha promoter polymorphism and early-onset psoriasis vulgaris in the northern Polish population suggests that the -238A variant may contribute not only to a predisposition to psoriasis vulgaris but also to the disease phenotype.
Asunto(s)
Polimorfismo Genético/genética , Regiones Promotoras Genéticas/genética , Psoriasis/genética , Factor de Necrosis Tumoral alfa/genética , Adulto , Anciano , Citocinas/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polonia/epidemiología , Psoriasis/epidemiologíaRESUMEN
The aim of the study was to compare the frequency of human leucocyte antigen-C (HLA-C) locus alleles in patients with psoriatic arthritis and in healthy controls in the same ethnic group in Poland, and to correlate them with age of onset of psoriatic skin changes and joints symptoms. HLA-C locus alleles of 41 patients and 80 controls were determined by a polymerase chain reaction (PCR) low-resolution method. The Cw*06 allele occurred more frequently (P adjusted for multiple comparison = 0.004) in patients with psoriatic arthritis than in controls. Patients who carried the HLA-Cw*06 allele had a significantly earlier mean age of onset of both psoriasis (P = 0.01) and arthritis (P = 0.008) compared with Cw*06-negative patients. Our results confirm the association between Cw*06 allele and psoriatic arthritis in the northern Poland population and suggest that the HLA-Cw*06 may determine not only the disease susceptibility, but also the age of onset of psoriatic arthritis.
Asunto(s)
Alelos , Artritis Psoriásica/genética , Frecuencia de los Genes/genética , Predisposición Genética a la Enfermedad , Antígenos HLA-C/genética , Polimorfismo Genético , Adolescente , Adulto , Factores de Edad , Estudios de Casos y Controles , Humanos , Masculino , PoloniaRESUMEN
Polymorphism of 18 STR loci specific to the human Y chromosome (DYS19, DYS388, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS426, DYS437, DYS438, DYS439, DYS460, GATA H4.1, DYS385 a/b, and YCAII a/b) was evaluated by means of a multiplex (octadecaplex) PCR reaction and capillary electrophoresis in a Polish population sample of 208 unrelated males. A total of 192 different haplotypes and 183 unique haplotypes were identified. The observed haplotype diversity was 0.998, while discrimination capacity was 92.3%. DYS389 was shown to be the most valuable in discrimination of similar haplotypes, whereas DYS388, DYS393, DYS426, and DYS438 did not affect the discrimination power of the multiplex.