The prevalence and treatment patterns of familial hypercholesterolemia among Thai patients with premature coronary artery disease.

OBJECTIVES: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder that is characterized by severe hypercholesterolemia. The prevalence of FH in Thailand has not been reported. Therefore, this study aimed to investigate the prevalence of FH and treatment patterns among Thai patients with premature coronary artery disease (pCAD). METHODS: A total of 1,180 pCAD patients at two heart centers from northeastern and southern Thailand between October 2018 and September 2020 were enrolled. FH was diagnosed using the Dutch Lipid Clinic Network (DLCN) criteria. pCAD was diagnosed in men aged < 55 years and women aged < 60 years. RESULTS: The prevalence of definite/probable FH, possible FH, and unlikely FH in pCAD patients was 1.36% (n = 16), 24.83% (n = 293), and 73.81% (n = 871), respectively. Definite/probable FH in pCAD patients had a significantly higher frequency of STEMI but a lower frequency of hypertension than those with unlikely FH. After discharge, most pCAD patients (95.51%) received statin therapy. Definite/probable FH patients had a higher frequency of high-intensity statin therapy than those with possible FH and unlikely FH. After follow-up for 3-6 months, approximately 54.72% of pCAD patients with DLCN scores ≥ 5 had a reduction in LDL-C > 50% from baseline. CONCLUSIONS: The prevalence of definite/probable FH, particularly possible FH, was high among pCAD patients in this study. The early diagnosis of FH among Thai pCAD patients should be performed for the early treatment and prevention of CAD.

Association of CELSR2, APOB100, ABCG5/8, LDLR, and APOE polymorphisms and their genetic risks with lipids among the Thai subjects.

Background: Hypercholesterolemia is a common cardiovascular risk factor. The aim of this study was to investigate the association of CELSR2 (rs629301), APOB100 (rs1367117), ABCG5/8 (rs6544713), LDLR (rs6511720), and APOE (rs429358, rs7412) polymorphisms, and their genetic risk scores with lipids among Thai subjects. Methods: A total of 459 study subjects (184 males, and 275 females) were enrolled. Blood pressure, serum lipids, and fasting blood sugar were measured. CELSR2 (rs629301), APOB100 (rs1367117), ABCG5/8 (rs6544713), and LDLR (rs6511720) polymorphisms were analyzed using PCR-HRM. APOE (rs429358, rs7412) polymorphism was analyzed using PCR-RFLP. Results: Total cholesterol (TC) levels were significantly higher in APOB100 AA genotype compared with GG, or AA + AG genotypes in total subjects. In addition, significantly higher concentrations of TC and low density lipoprotein cholesterol (LDL-C) were observed in APOE4 carriers compared to APOE2 carriers in total subjects, males, and females. The significantly higher concentrations of TC were observed in APOE4 carriers compared to APOE3 carriers in females. Moreover, the concentrations of TC, and LDL-C were significantly increased with genetic risk scores of APOB100, and APOE polymorphisms in total subjects, and females. There was no association between CELSR2 (rs629301), ABCG5/8 (rs6544713), and LDLR (rs6511720) polymorphisms and serum lipids. Conclusion: APOB100 (rs1367117), and APOE (rs429358, rs7412) but not CELSR2 (rs629301), ABCG5/8 (rs6544713), and LDLR (rs6511720) polymorphisms were associated with serum lipids. The cumulative risk alleles of APOB100 (rs1367117), and APOE (rs429358, rs7412) polymorphisms could enhance the elevated concentrations of TC, and LDL-C, and they may be used to predict severity of hypercholesterolemia among Thai subjects.

Allicin and Capsaicin Ameliorated Hypercholesterolemia by Upregulating LDLR and Downregulating PCSK9 Expression in HepG2 Cells.

Hypercholesterolemia is a common cause of cardiovascular diseases (CVDs). Although allicin and capsaicin possess hypolipidemic effects through several molecular mechanisms, their effects on LDLR and PCSK9 expression are still unknown. This study aimed to investigate the effects of allicin and capsaicin on LDLR and PCSK9 expression in HepG2 cells. The effects of allicin and capsaicin on cell viability were evaluated by MTT assay and trypan blue exclusion assay. Low-density lipoprotein receptor (LDLR) levels and LDL uptake were determined by flow cytometry and confocal laser scanning microscopy (CLSM), respectively. RT-qPCR and Western blot analyses were performed to evaluate the expression of PCSK9, LDLR, SREBP-2, and HNF1α. ELISA was used to measure PCSK9 levels in culture media. Allicin and capsaicin increased the protein expression levels of LDLR via activation of the transcription factor SREBP2. However, allicin and capsaicin decreased the expression of PCSK9 protein and the secretion of PCSK9 in culture media via the suppression of HNF1α. Moreover, allicin and capsaicin increased LDL uptake into HepG2 cells. The efficacies of the hypolipidemic effects of allicin (200 µM) and capsaicin (200 µM) were comparable to that of atorvastatin (10 µM) in this study. In conclusion, allicin and capsaicin possessed hypolipidemic effects via the upregulation of LDLR and downregulation of PCSK9 expression, thereby enhancing LDL uptake into HepG2 cells. This indicates that allicin and capsaicin should be used as potent supplements to ameliorate hypercholesterolemia.

Paraoxonase 1 (PON1) L55M and Q192R polymorphisms are not associated with chronic kidney disease in Thai individuals with type 2 diabetes.

BACKGROUND: Decreased paraoxonase 1 (PON1) activity and PON1 polymorphisms have been found to be associated with chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM). OBJECTIVE: This study aimed to investigate the association of the PON1 L55M and Q192R polymorphisms with CKD in T2DM, as well as their relationship with PON1 activity. METHODS: A total of 166 T2DM patients, including 83 CKD patients and 83 non-CKD patients, were recruited. Biochemical parameters and paraoxonase (PONase) and arylesterase (AREase) activities were measured. The PON1 L55M and Q192R polymorphisms were analysed by a polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. Data were analysed using the chi-square test, Student's t-test and logistic regression analysis. RESULTS: Total cholesterol, TGs, LDL-C and Cr were significantly higher in CKD patients than in non-CKD patients. In contrast, the estimated glomerular filtration rate (eGFR) and AREase activity were significantly lower in CKD patients than in non-CKD patients (P < .05). The genotype and allele frequencies of the PON1 L55M and Q192R polymorphisms were not significantly different between CKD and non-CKD patients. Multivariate logistic regression analysis showed no association between the PON1 L55M and Q192R polymorphisms and CKD in T2DM. In addition, among all patients, patients with the PON1 LM genotype had significantly lower PONase activity than those with the LL genotype (P < .05). Among all patients, CKD patients and non-CKD patients, those with the PON1 RR genotype had significantly higher PONase activity but lower AREase activity than patients with the QR and QQ genotypes (P < .05). CONCLUSIONS: PON1 activity was influenced by the PON1 L55M and Q192R polymorphisms. However, the PON1 L55M and Q192R polymorphisms may not be considered genetic biomarkers for CKD in T2DM.