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Prognostic predictive value of TLR4 polymorphisms in Han Chinese population with hypertrophic cardiomyopathy.
Kaohsiung Journal of Medical Sciences 2018 October
Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiac disease and is an important cause of sudden death in patients of all ages. The aim of this study was to find out whether Toll-like receptor-4 (TLR4) polymorphism is associated with HCM. To explore the association between TLR4 gene polymorphisms and HCM, 486 HCM patients and 214 healthy controls were enrolled in a case-control study of Chinese Han population. Two single nucleotide polymorphisms (SNPs) in the promoter region of TLR4 gene, -728G > C (rs11536865) and -2081G > A (rs10983755), were genotyped by PCR restriction fragment length polymorphism (PCR-RFLP). The associations between TLR4 SNPs and overall survival (OS) of HCM patients were analyzed by the Kaplan-Meier estimation method and Cox proportional hazards regression analysis. Serum TLR4 level was determined by ELISA. Our results showed that the C allelic frequency of -728G > C and A allelic frequency of -2081G > A were higher in HCM patients than those in controls (P < 0.001). The ratios of genotype frequencies for both SNPs were associated with HCM susceptibility under three genetic models (P < 0.01). Two SNPs were also associated with the OS in HCM patients (P < 0.001). The CC genotype of -728G > C and AA genotype of -2081G > A were associated with poor prognosis of HCM (P < 0.001). Moreover, HCM patients had a higher serum TLR4 level compared with the controls (242.6 pg/ml versus 135.7 pg/ml, P = 0.027). In addition, significant associations were observed between CC genotype of -728G > C or AA genotype of -2081G > A and plasma TLR4 level (P < 0.01). The results of this study indicated that TLR4 polymorphisms may be a genetic susceptibility factor for HCM in the Han Chinese population.
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