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Independent Genetic Risk Factors (independent + genetic_risk_factor)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

The combination of polymorphisms within MCP-1 and IL-1, associated with ulcerative colitis

INTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 3 2009
K.-S. Li
Summary Monocyte chemoattractant protein-1 (MCP-1) is a chemokine involved in monocyte recruitment to sites of inflammation. Raised level of MCP-1 has been widely demonstrated in the intestinal mucosa of patients with ulcerative colitis (UC), suggesting an important role of MCP-1 in the pathogenesis of UC. The ,2518A/G polymorphism in the promoter region of MCP-1 gene affecting its transcriptional activation has been reported recently. In order to assess the potential role of this polymorphism in UC, we examined its distribution in 162 unrelated UC patients and 203 healthy controls. In addition, considering the gene regulatory association between interleukin-1, (IL-1,) and MCP-1, we further examined whether the gene polymorphisms between MCP-1 and IL-1, exert synergetic effects on risk of UC. Our results show that the distribution of MCP-1 genotype or allele frequencies between UC patients and controls was not significantly different; however, the association between the polymorphism of MCP-1 ,2518 GG and the polymorphism of IL-1,,511 T in UC patients is significant (OR 2.062, 95% CI 1.034,4.113, P = 0.038). This is the first report describing the association between MCP-1 polymorphism and UC, and our data suggest that the MCP-1 ,2518 polymorphism itself does not represent an independent genetic risk factor for UC. In contrast, the combination polymorphisms between MCP-1 and IL-1, can increase UC risk significantly, which might help us understand the molecular mechanism underlying the development of UC. [source]

Human platelet alloantigens (HPA) 1, HPA2, HPA3, HPA4, and HPA5 polymorphisms in sickle cell anemia patients with vaso-occlusive crisis

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2009
Abeer M. Al-Subaie
Abstract Objectives:, Vaso-occlusive crisis (VOC) is a significant cause of morbidity and mortality in sickle cell anemia (SCA) patients. Insofar as polymorphism in human platelet alloantigen (HPA) exhibit a prothrombotic nature, we hypothesized that specific HPA polymorphic variants are associated with VOC. We investigated the distribution of HPA1, HPA2, HPA3, HPA4, and HPA5 alleles genotypes among VOC and non-VOC control SCA patients. Patients/methods:, This was a case,control study. Study subjects comprised SCA patients with (VOC group; n = 127) or without (Steady-state group; n = 130) VOC events. HPA genotyping was done by PCR-SSP. Results:, Significantly higher frequencies of HPA-2b, HPA-3b, and HPA-5b alleles, and marked enrichment of HPA-3b/3b, HPA-5a/5b, and HPA-5b/5b genotypes, were seen in VOC than in control SCA patients. Taking homozygous wild-type genotypes as reference, univariate analysis identified HPA-3a/3b, HPA-3b/3b, and HPA-5b/5b to be associated with VOC. Multivariate analysis confirmed the independent association of only HPA-3a/3b and HPA-3b/3b genotypes with VOC. HPA-3 genotypes were significantly correlated with VOC frequency, type, and medication, and requirement for hospitalization. While both HPA 3a/3b (P = 0.002; OR = 2.94; 95% CI = 1.49,5.77) and 3b/3b (P = 0.006; OR = 3.16; 95% CI = 1.40,7.17) genotypes were associated with need for hospitalization, only HPA-3b/3b was associated with VOC frequency, type (localized vs. generalized), and medication (narcotics vs. NSAIDs). Conclusion:, This confirms the association of HPA polymorphisms with SCA VOC, of which HPA-3 appears to be independent genetic risk factors for SCA VOC. [source]

A common haplotype of the C-C chemokine receptor 2 gene and HLA-DRB1*0301 are independent genetic risk factors for Löfgren's syndrome

JOURNAL OF INTERNAL MEDICINE, Issue 5 2008
P. Spagnolo
Abstract. Aim., Sarcoidosis is a heterogeneous disorder with a strong genetic influence. Genetic factors are also thought to influence disease severity and outcome. We sought to determine whether polymorphisms within CCR2 gene predispose to Löfgren's syndrome , a clinically and genetically distinct sarcoidosis phenotype , and, importantly, whether this association is independent of the known association with the HLA-DRB1*0301 allele. Methods., We investigated 5 CCR2 variants and HLA-DRB1*0301 by sequence-specific primer (SSP) polymerase chain reaction (PCR) in 176 Spanish (76 Löfgren's syndrome, 100 controls) and 387 Swedish subjects (126 Löfgren's syndrome, 77 non-Löfgren sarcoidosis, 184 controls). Results., One of the deduced haplotypes (CCR2 haplotype 2) was associated with Löfgren's syndrome in both Spanish (OR: 2.03, uncorrected P = 0.02; permuted P = 0.041 vs. controls) and Swedish patients (OR: 3.02, uncorrected P = 0.0007; permuted P = 0.0027 vs. non-Löfgren sarcoidosis; OR: 2.46, uncorrected P = 0.0005; permuted P = 0.0031 vs. controls). HLA-DRB1*0301 allele frequency was also increased in Spanish (OR: 3.52, P = 0.0004 vs. controls) and Swedish patients with Löfgren's syndrome (OR: 10.98, P < 0.0001 vs. non-Löfgren sarcoidosis, OR: 7.71, P < 0.0001 vs. controls). Finally, multivariate analysis revealed that the CCR2 association was independent of HLA-DRB1*0301 in both Spanish (P = 0.02 vs. controls) and Swedish cohorts (P = 0.002 vs. non-Löfgren sarcoidosis, P = 0.001 vs. controls). Conclusions., This study confirms that CCR2 haplotype 2 and HLA-DRB1*0301 are independent genetic risk factors for Löfgren's syndrome. [source]