RESUMO
OBJECTIVE: To explore the distribution of Toll-like receptors gene polymorphisms in inflammatory bowel disease (IBD) in Chinese Han patients and Caucasians. METHODS: The toll-like receptor 2 (TLR2) genes Arg677Trp and Arg753Glu, TLR4 genes Asp299Gly and Thr399Ile, and TLR9 gene 1237T/C polymorphisms were genotypes in 113 patients with IBD and 120 age and gender-matched healthy controls by the analyses of polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). A meta-analysis was performed to test whether TLR4 Asp299Gly and Thr399Ile polymorphisms were associated with ulcerative colitis (UC) or Crohn's disease (CD) susceptibility and whether 299Gly carriage was associated with phenotypes of CD patients in the Caucasian population. RESULTS: We found two carriers of TLR9 1237C in UC patients, one carrier in CD patients and one in healthy controls respectively (CD: P = 0.361; UC: P = 0.569). There was no statistically significant difference in both allelic and genotypic frequencies. The mutant genotypes of TLR2 gene Arg677Trp and Arg753Glu, TLR4 gene Asp299Gly and Thr399Ile were not found in either the IBD patients or the healthy controls. The TLR4 299G allele showed a significant association with CD and UC in Caucasian population (OR = 1.29, 95%CI: 1.08 - 1.54, P = 0.004 and OR = 1.28, 95%CI: 1.08 - 1.51, P = 0.004 respectively). Similar association was detected between T399I polymorphism and susceptibility to IBD (OR = 1.37, 95%CI: 1.12 - 1.68, P = 0.002 and OR = 1.46, 95%CI: 1.13 - 1.88, P = 0.003 respectively). However, no significant association was identified between CD phenotypes and 299Gly carriage. CONCLUSION: TLR2 genes Arg677Trp and Arg753Glu, TLR4 genes Asp299Gly and Thr399Ile and TLR9 gene 1237T/C polymorphisms are not associated with IBD in Chinese Han patients. In Caucasians, both TLR4 299G and 399I confer a significant risk for developing CD and UC. The contribution of genetic determinants may differ significantly between ethnicities.
Assuntos
Doenças Inflamatórias Intestinais/etnologia , Doenças Inflamatórias Intestinais/genética , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética , Adolescente , Adulto , Idoso , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , Doença de Crohn/etnologia , Doença de Crohn/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo Genético , População Branca/genética , Adulto JovemRESUMO
BACKGROUND: Super-responders (SRs) to cardiac resynchronization therapy (CRT) regain near-normal or normal cardiac function. The extent of cardiac synchrony of SRs and whether continuous biventricular (BIV) pacing is needed remain unknown. The aim of this study was to evaluate the cardiac electrical and mechanical synchrony of SRs. METHODS: We retrospectively analyzed CRT recipients between 2008 and 2016 in 2 centers to identify SRs, whose left ventricular (LV) ejection fraction was increased to ≥50% at follow-up. Cardiac synchrony was evaluated in intrinsic and BIV-paced rhythms. Electrical synchrony was estimated by QRS duration and LV mechanical synchrony by single-photon emission computed tomography myocardial perfusion imaging. RESULTS: Seventeen SRs were included with LV ejection fraction increased from 33.0â±â4.6% to 59.3â±â6.3%. The intrinsic QRS duration after super-response was 148.8â±â30.0âms, significantly shorter than baseline (174.8â±â11.9âms, Pâ=â0.004, tâ=â-3.379) but longer than BIV-paced level (135.5â±â16.7âms, Pâ=â0.042, tâ=â2.211). Intrinsic LV mechanical synchrony significantly improved after super-response (phase standard deviation [PSD], 51.1â±â16.5° vs. 19.8â±â8.1°, Pâ<â0.001, tâ=â5.726; phase histogram bandwidth (PHB), 171.7â±â64.2° vs. 60.5â±â22.9°, Pâ<â0.001, tâ=â5.376) but was inferior to BIV-paced synchrony (PSD, 19.8â±â8.1° vs. 15.2â±â6.4°, Pâ=â0.005, tâ=â3.414; PHB, 60.5â±â22.9° vs. 46.0â±â16.3°, Pâ=â0.009, tâ=â3.136). CONCLUSIONS: SRs had significant improvements in cardiac electrical and LV mechanical synchrony. Since intrinsic synchrony of SRs was still inferior to BIV-paced rhythm, continued BIV pacing is needed to maintain longstanding and synchronized contraction.