Prognostic predictive value of TLR4 polymorphisms in Han Chinese population with hypertrophic cardiomyopathy

Abstract

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.

Genetic Polymorphisms that Playing Role in Development of Hypertrophic Cardiomyopathy

“…One person in 500 people worldwide is affected by this disease [6]. HCM is a common heterogeneous disease with high morbidity and mortality in the elderly, and it is characterized by enlarged heart, abnormally thickened left ventricular walls, and reduced chamber capacity [8]. Histologically, in this disease, characterized by left ventricular thickness resulting from cardiomyocyte hypertrophy, cardiomyocytes lose their cleavage ability in the first week after birth.…”

“…This disease is thought to be caused by contractile proteins encoding genes that cause contractile dysfunction and then hypertrophy. Familial HCM, defined as an autosomal dominant disorder, is usually disseminated by incomplete penetrance due to heterozygous pathogenic gene mutations [8]. HCM is a genetically transmitted, cardiovascular disease with heterogeneous clinical features.…”

“…Accordingly, it is believed that TLR4 gene polymorphisms affect the progression of natural immunity or inflammation, thus altering the expression level of TLR4, which is involved in the development of HCM. When studies with larger populations are performed, different results are likely to occur [8]. Primer sequences for −728G > C and −2081G > A gene polymorphisms are presented in Table 1.…”

Correlations of IL-1 and IL-6 Gene polymorphisms with hypertrophic cardiomyopathy

“…They are important factors in monitoring and controlling the development of diseases [7,8]. HCM has been proven to be affected by the polymorphism of multiple genes like angiotensin-converting enzyme-related genes [9] and TLR4 [10]. IL-1 and IL-6 are important pro-inflammatory and pro-immune substances, that play a vital role in HCM, but the relationships of their polymorphisms with the disease have not been reported.…”