RESUMO
BACKGROUND: The serum level of osteoprotegerin (encoded by OPG or TNFRSF11B) was previously shown to be increased in patients with ischemic stroke. A single nucleotide polymorphism rs3134069 in the TNFRSF11B gene was previously associated with ischemic stroke in a population of diabetic patients in Italy. It remains to be determined whether rs3134069 is associated with ischemic stroke in the general population or populations without diabetes. MATERIALS AND METHODS: We genotyped rs3134069 and performed a case-control association study to test whether rs3134069 is associated with ischemic stroke in 2 independent Chinese Han populations, including a China-Central population with 1629 cases and 1504 controls and a China-Northern population with 1206 cases and 720 controls. RESULTS: rs3134069 showed significant association with ischemic stroke in the China-Central population (P = 9.24 × 10-3, odds ratio [OR] = 1.50). The association was replicated in the independent China-Northern population (P = 2.45 × 10-4, OR = 1.53). The association became more significant in the combined population (P = 7.09 × 10-6, OR = 1.41). The associations remained significant in the male population, female population, and population without type 2 diabetes. Our expression quantitative trait loci analysis found that the minor allele C of rs3134069 was significantly associated with a decreasedexpression level of TNFRSF11B (P = .002). CONCLUSIONS: This study demonstrates that rs3134069 in TNFRSF11B increases risk of ischemic stroke by decreasing TNFRSF11B expression.
Assuntos
Isquemia Encefálica/genética , Osteoprotegerina/genética , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/genética , Adulto , Idoso , Povo Asiático/genética , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etnologia , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , China/epidemiologia , Diabetes Mellitus Tipo 2/etnologia , Diabetes Mellitus Tipo 2/genética , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Locos de Características Quantitativas , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etnologiaRESUMO
The interleukin 1 family plays an important role in the immune and inflammatory responses. Coronary artery disease (CAD) is a chronic inflammatory disease. However, the genetic association between IL-37, the seventh member of the IL-1 family, and CAD is unknown. Here we show that a single nucleotide polymorphism in the IL-37 gene (rs3811047) confers a significant risk of CAD. We have performed an association analysis between rs3811047 and CAD in two independent populations with 2,501 patients and 3,116 controls from China. Quantitative RT-PCR analysis has been performed to determine if the IL-37 expression level is influenced by rs3811047. We show that the minor allele A of rs3811047 is significantly associated with CAD in two independent populations under a recessive model (Padj = 5.51 × 10-3/OR = 1.56 in the GeneID Northernern population and Padj = 1.23 × 10-3/OR = 1.45 in the GeneID Central population). The association became more significant in the combined population (Padj = 9.70 × 10-6/OR = 1.47). Moreover, the association remains significant in a CAD case control population matched for age and sex. Allele A of rs3811047 shows significant association with a decreased mRNA expression level of IL-37 (n = 168, P = 3.78 × 10-4). These data suggest that IL37 is a new susceptibility gene for CAD, which provides a potential target for the prevention and treatment of CAD.
