scholarly journals Association between the TIMD4-HAVCR1 variants and serum lipid levels, coronary heart disease and ischemic stroke risk and atorvastatin lipid-lowering efficacy

2018 ◽  
Vol 38 (1) ◽  
Author(s):  
Qing-Hui Zhang ◽  
Rui-Xing Yin ◽  
Wu-Xian Chen ◽  
Xiao-Li Cao ◽  
Yu-Ming Chen

Little is known about the association of the TIMD4 (T-cell immunoglobulin and mucin domain 4 gene)-HAVCR1 (hepatitis A virus cellular receptor 1) variants and lipid metabolism, the risk of coronary heart disease (CHD) and ischemic stroke (IS). The present study aimed to determine the TIMD4-HAVCR1 variants, their haplotypes and gene–environment interactions on serum lipid levels, the risk of CHD and IS, and the lipid-lowering efficacy of atorvastatin in a southern Chinese Han population. Genotypes of three variants in 622 controls, 579 CHD, and 546 IS patients were determined by the Snapshot technology. Atorvastatin calcium tablet (20 mg/day) was given in 724 hyperlipidemic patients for 8 weeks after genotyping. The rs12522248 genotypic and allelic frequencies were different between controls and patients, and were associated with the risk of CHD and IS. The rs1501908G-rs12522248T-rs2036402T haplotype was associated with an increased risk of CHD; the G-C-T haplotype was associated with lower risk of CHD; and the C-C-C haplotype was associated with an increased risk of IS. Variants and their haplotypes in controls were associated with triglyceride (rs1501908), low-density lipoprotein cholesterol (LDL-C, rs1501908, G-T-T), high-density lipoprotein cholesterol (HDL-C, rs12522248, C-C-C) and the ratio of total cholesterol (TC) to HDL-C (C-C-C). Interactions of rs1501908- and rs2036402-alcohol (HDL-C); rs1501908- and rs12522248-high body mass index (hBMI, ≥24 kg/m2; TC); and TIMD4-HAVCR1 variants-atorvastatin on several lipid parameters were detected. Interactions of rs12522248TC/CC-hBMI, G-T-T-, and C-C-C-smoking on the risk of CHD; and C-C-C-smoking, C-C-C-, and G-C-T-hBMI on the risk of IS were also observed. These findings suggest that the TIMD4-HAVCR1 variants may be the genetic risk factors for CHD and IS.

2020 ◽  
Vol 48 (7) ◽  
pp. 030006052093465
Author(s):  
Yunxue Bai ◽  
Ruicheng Huang ◽  
Lagen Wan ◽  
Rui Zhao

Objective The CYP2C19 genetic variation may be involved in the development of atherosclerotic cardiovascular disease (ASCVD). Serum lipid levels are important risk factors for ASCVD, but the effect of the CYP2C19 gene on serum lipid metabolism remains unclear. This retrospective cohort study investigated the relationship between the CYP2C19 gene polymorphism and serum lipid levels in patients with ischemic stroke (IS). Methods IS patients (n = 230) and control subjects (n = 100) were enrolled. All patients were diagnosed with IS via clinical manifestations and brain magnetic resonance imaging. All patients were genotyped. Results Triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and apolipoprotein B (ApoB) levels were significantly higher and high-density lipoprotein-cholesterol (HDL-c) and apolipoprotein A1 (ApoA1) levels were significantly lower in the IS group compared with the control group. Lower ApoA1 levels and higher ApoB levels were significant predictive factors for IS. Patients with higher ApoB levels had a higher risk of IS recurrence. Compared with extensive metabolizers, intermediate and poor CYP2C19 metabolizers had a higher risk of IS recurrence. Conclusions Our study indicates CYP2C19 gene polymorphisms are related to lipid metabolism in patients with IS. IS patients who are poor CYP2C19 metabolizers may have a higher risk of disease recurrence.


Oncotarget ◽  
2017 ◽  
Vol 8 (42) ◽  
pp. 72801-72817 ◽  
Author(s):  
Liu Miao ◽  
Rui-Xing Yin ◽  
Feng Huang ◽  
Wu-Xian Chen ◽  
Xiao-Li Cao ◽  
...  

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Tingting Wang ◽  
Li Sun ◽  
Li Xu ◽  
Ting Zhao ◽  
Jie Feng ◽  
...  

Abstract Background Dyslipidemia is a predisposing factor for coronary heart disease (CHD). High-intensity statin therapy is recommended as secondary prevention. ABCB1 and SLCO1B1 genes influence the efficacy and safety of statins. Xinjiang is a multi-ethnic area; however, little is known about the prevalence of dyslipidemia and gene polymorphisms of ABCB1 and SLCO1B1 in minority groups with CHD. Objective To measure levels of lipid and apolipoprotein and the prevalence of dyslipidemia and gene polymorphisms of ABCB1, SLCO1B1 in Han, Uygur, Kazak, Hui, Tatar, Kirgiz, and Sibe populations with CHD in Xinjiang. Methods This descriptive retrospective study compares lipid levels in ethnic groups using Kruskal-Wallis test or analysis of variance. The study compared gene polymorphisms and the prevalence of dyslipidemia among different ethnic groups using the chi-square test. The lipid profiles in plasma were measured before lipid-lowering therapy using commercially available kits. Genotyping of SLCO1B1 and ABCB1 variants was performed using sequencing by hybridization. Results A total of 2218 patients were successfully screened, including 1044 Han, 828 Uygur, 113 Kazak, 138 Hui, 39 Tatar, 36 Kirgiz, and 20 Sibe patients. The overall mean age was 61.8 ± 10.8 years, and 72.5% of participants were male. Dyslipidemia prevalence in these ethnic groups was 42.1, 49.8, 52.2, 40.6, 48.7, 41.7, and 45.0%, respectively. The prevalence of dyslipidemia, high total cholesterol (TC), high triglycerides (TG), and high low density lipoprotein cholesterol (LDL-C) differed significantly among the groups (P = 0.024; P < 0.001; P < 0.001; P < 0.001, respectively). For the Han group, high LDL-C, high TC, and high TG prevalence differed significantly by gender (P = 0.001, P = 0.022, P = 0.037, respectively). The prevalence of high TC, high TG, and low high density lipoprotein cholesterol (HDL-C) differed significantly by gender in the Uygur group (P = 0.006, P = 0.004, P < 0.001, respectively). The prevalence of high TC in Hui patients significantly differed by gender (P = 0.043). These findings suggest that polymorphisms in ABCB1 and C3435T differ significantly across ethnicities (P < 0.001). Conclusions The prevalences of dyslipidemia, high TC, high TG, and high LDL-C in Han, Uygur, Kazak, Hui, Tatar, Kirgiz, and Sibe CHD patients in Xinjiang differed concerning ethnicity. Ethnic, gender, and lifestyle were the key factors that affected the lipid levels of the population. The prevalence of polymorphisms of ABCB1 and C3435T significantly differed across ethnicities. These findings will aid the selection of precision lipid-lowering medications and prevention and treatment of CHD according to ethnicity in Xinjiang.


PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4637 ◽  
Author(s):  
Xingchen Zhou ◽  
Wu Zhu ◽  
Minxue Shen ◽  
Yijing He ◽  
Cong Peng ◽  
...  

Background Acitretin is a second-generation synthetic retinoid, and is widely used for treating the severe psoriasis vulgaris. However, it should be chosen with caution for its cardiovascular risk, and it is reported that acitretin may increase the serum lipids. The purpose of this study is to investigate the relationship between the Frizzled-related proteins 4 (SFRP4) rs1802073 polymorphism and the changes of serum lipids in Chinese psoriatic patients during the treatment with acitretin. Methods In our study, 100 psoriatic patients were recruited systematically treated with acitretin (30 mg/day) for at least eight weeks. Data of the patients’ demographic and clinical characteristics and the results of serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were collected pre- and post-treatment. Results A total of 84 psoriatic patients were enrolled and divided into three groups by SFRP4 rs1802073 genotypes. The patients who carried with TT genotype had maintained levels of TG and LDL-C after acitretin treatment, while patients with GG/GT genotypes had significantly elevated levels of serum TG and LDL-C compared to the TT genotype (ΔTG%: 27.53 ± 59.13 vs −1.47 ± 37.79, p = 0.026, ΔLDL-C%: 10.62 ± 26.57 vs −1.29 ± 17.07, p = 0.042). The association of rs1802073 with TG and LDL-C profiles remained significant after adjusting for age, gender, and body mass index. Although without significance, the pre-post change in serum level of TC across rs1802073 GG/GT genotypes demonstrated a trend similar to TG and LDL, and the serum level of HDL-C demonstrated a trend opposite to TG, TC and LDL. Conclusions Our results demonstrated that SFRP4 rs1802073 polymorphism was found to be associated with elevated serum lipid levels after acitretin treatment, and it may serve as a genetic marker of safe and precise treatment for individual psoriatic patients.


2020 ◽  
Vol 27 (15) ◽  
pp. 1617-1626 ◽  
Author(s):  
Roshni Joshi ◽  
S Goya Wannamethee ◽  
Jorgen Engmann ◽  
Tom Gaunt ◽  
Deborah A Lawlor ◽  
...  

Aims Elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for cardiovascular disease; however, there is uncertainty about the role of total triglycerides and the individual triglyceride-containing lipoprotein sub-fractions. We measured 14 triglyceride-containing lipoprotein sub-fractions using nuclear magnetic resonance and examined associations with coronary heart disease and stroke. Methods Triglyceride-containing sub-fraction measures were available in 11,560 participants from the three UK cohorts free of coronary heart disease and stroke at baseline. Multivariable logistic regression was used to estimate the association of each sub-fraction with coronary heart disease and stroke expressed as the odds ratio per standard deviation increment in the corresponding measure. Results The 14 triglyceride-containing sub-fractions were positively correlated with one another and with total triglycerides, and inversely correlated with high-density lipoprotein cholesterol (HDL-C). Thirteen sub-fractions were positively associated with coronary heart disease (odds ratio in the range 1.12 to 1.22), with the effect estimates for coronary heart disease being comparable in subgroup analysis of participants with and without type 2 diabetes, and were attenuated after adjustment for HDL-C and LDL-C. There was no evidence for a clear association of any triglyceride lipoprotein sub-fraction with stroke. Conclusions Triglyceride sub-fractions are associated with increased risk of coronary heart disease but not stroke, with attenuation of effects on adjustment for HDL-C and LDL-C.


2002 ◽  
Vol 30 (2) ◽  
pp. 68-73 ◽  
Author(s):  
J. M. Ordovas

Strategies for disease prevention can have a major impact on people's health. However, major gaps exist in our knowledge with regard to nutritional adequacy, nutrient-disease interactions, nutrient-gene interactions, and effective strategies for implementation of dietary recommendations which have the potential to decrease the disease burden and to contribute to successful aging of the population. Coronary heart disease is one of the major causes of mortality in the world. We have sound evidence that high levels of low-density lipoprotein cholesterol (LDL-C) and low levels of high-density lipoprotein cholesterol (HDL-C) are associated with increased risk of coronary heart disease. Lipoprotein concentrations are associated with environmental variables such as diet and lifestyle, but genetics also play a significant role. We have examined polymorphisms at candidate loci to determine their usefulness as markers for dietary responses. A G/A polymorphism 75 bp upstream from the gene encoding apolipoprotein AI (APOA1) has been described in ~ 30% of the population. Our studies show that this polymorphism is associated with variability in the HDL-C response to dietary fat, specifically to polyunsaturated fatty acids (PUFA) in the diet. Carriers of the A allele respond to increases in dietary PUFA with elevations in HDL-C levels, probably due to altered interactions of transcription factors with the mutated promoter. Therefore carriers of the A allele can potentially decrease their atherogenic risk by consuming high-PUFA diets. Likewise, we have examined the interaction between other dietary habits, such as alcohol drinking, and variability at the APOE locus, and have demonstrated that the classical associations between APOE polymorphism and LDL-C levels are observed primarily in those subjects who consume alcohol. Moreover, we have found a subgroup of the population, APOE4 carriers, for whom drinking alcohol may exert detrimental effects on lipid metabolism. This knowledge will contribute towards the development of more effective personalized dietary recommendations.


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