Homocysteine, hyperhomocysteinemia, and H-type hypertension.

Homocysteine (Hcy) is a sulphur-containing nonessential amino acid derived from the intermediate metabolites of methionine. Methionine is obtained from dietary proteins, such as poultry, meat, eggs, seafood, and dairy products. Abnormalities in Hcy metabolic pathways, deficiencies in dietary methionine, folate, and vitamins B12, B6, and B2 and genetic defects, polymorphisms, or mutations in Hcy metabolism-related enzymes may lead to an increase in plasma Hcy levels. Generally, a plasma Hcy level higher than 10 or 15 µmol/L has been defined as hyperhomocysteinemia (HHcy). An individual with essential hypertension complicated with HHcy is considered to have H-type hypertension (HTH). Currently, HHcy is considered a novel independent risk factor for various cardiovascular diseases. To provide a useful reference for clinicians, the research progress on Hcy, HHcy, and HTH in recent years was systematically reviewed here, with a focus on the source and metabolic pathways of Hcy, plasma Hcy levels and influencing factors, detection methods for plasma Hcy levels, relationship between Hcy concentration and hypertension, pathogenesis of HTH, cardiovascular complications of HTH, and treatment of HTH.

Application of the metal ions as potential population biomarkers for wastewater-based epidemiology: estimating tobacco consumption in Southern China.

Wastewater-based epidemiology (WBE) is an objective approach for the estimation of population-level exposure to a wide range of substances, in which the use of a population biomarker (PB) could significantly reduce back-calculation errors. Although some endogenous or exogenous compounds such as cotinine and other hormones have been developed as PBs, more PBs still need to be identified and evaluated. This study aimed to propose a novel method to estimate population parameters from the mass load of metal ion biomarkers in wastewater, and estimate the consumption of tobacco in 24 cities in Southern China using the developed method. Daily wastewater samples were collected from 234 wastewater treatment plants (WWTPs) in 24 cities in Southern China. Atomic absorption spectroscopy (AAS) was applied to determine the concentrations of common health-related metal ions in wastewater, including sodium (Na), potassium (K), magnesium (Mg), calcium (Ca), iron (Fe), and zinc (Zn), and compared them with the daily mass load of cotinine corresponding to catchment populations. The concentrations of cotinine in wastewater samples were measured using liquid chromatography-tandem mass spectrometry. There were clear and strong correlations between the target metal ion equivalent population and census data. The correlation coefficients (R) were RK = 0.78, RNa = 0.66, RCa = 0.81, RMg = 0.77, and RFe = 0.69, at p < 0.01 and R2 > 0.6. Subsequently, the combination of WBE and metal ion PBs was used to estimate tobacco consumption. Daily consumption of nicotine was estimated to be approximately 1.76 ± 1.19 mg/d/capita, equivalent to an average of 13.0 ± 8.75 cigarettes/d being consumed by smokers. The data on tobacco consumption in this study were consistent with those in traditional surveys in Southern China. The metal ion potassium is an appropriate PB for reflecting the real-time population and could be used to evaluate the tobacco consumption in WBE study.

Differential effects of hyperhomocysteinemia on the lipid profiles and lipid ratios between patients with and without coronary artery disease: A retrospective observational study.

This study aimed to investigate the differential effects of hyperhomocysteinemia (HHcy) on lipid profiles and lipid ratios between patients with coronary artery disease (CAD) and without CAD. The data of 872 CAD patients and 774 non-CAD controls were extracted from the information system of hospitalized patients. Serum homocysteine (Hcy), total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) AI, and ApoB concentrations were detected. HHcy was defined as a serum level of Hcy ≥ 15 µmol/L. The CAD patients had lower levels of HDL-C and ApoAI and higher levels of Hcy than the controls (P < .05). Serum TGs and HDL-C were negatively correlated with Hcy in controls. Serum HDL-C and ApoAI were negatively correlated with Hcy, and the ratios of TC/HDL-C, TG/HDL-C, LDL/HDL-C, and ApoB/ApoAI were positively correlated with Hcy in the CAD patients (P < .05). Although the trends for HHcy to decrease the lipid profiles were not different between the CAD and controls (Pinteraction > 0.05), CAD with HHcy had lower HDL-C and ApoAI levels than those of subjects with normal Hcy; controls with HHcy had lower TC, LDL-C, and ApoB levels than those of subjects with normal Hcy (P < .05). There were different HHcy trends affecting the ratios of TC/HDL-C and LDL/HDL-C between the CAD patients and controls (Pinteraction for TC/HDL-C = 0.025; Pinteraction for LDL/HDL-C = 0.033). CAD patients with HHcy had a higher ratio of TC/HDL-C (P = .022) and LDL/HDL-C (P = .045) than those of patients with normal Hcy, but in the controls, the subjects with HHcy exhibited a trend toward a decreased ratio of TC/HDL-C (P = .481) and LDL/HDL-C (P = .303). There were differential effects of HHcy on the lipid ratios between CAD and non-CAD patients. HHcy was related to higher ratios of TC/HDL-C and LDL/HDL-C in patients with CAD.

High expression of protein phosphatase 2 regulatory subunit B'' alpha predicts poor outcome in hepatocellular carcinoma patients after liver transplantation.

BACKGROUND: Protein phosphatase 2 regulatory subunit B'' alpha (PPP2R3A) gene has been reported in other tumors, but the influence of PPP2R3A gene expression on the occurrence, development, and prognosis of hepatocellular carcinoma (HCC) remains unclear. AIM: To investigate whether the PPP2R3A gene could be used to predict tumor recurrence and survival of HCC patients after liver transplantation (LT). METHODS: Diseased liver tissues of HCC patients after LT were collected as well as their clinical data and follow-up information. The immunohistochemical method was used to detect the expression of PPP2R3A protein in the tissues of 108 patients with primary liver cancer. The χ 2 test was used to analyze the relationship between PPP2R3A protein expression levels and the clinicopathological features of tumors. The Kaplan-Meier method was used to analyze overall postoperative survival. The COX proportional hazard model was used to analyze adverse prognostic factors. RESULTS: Immunohistochemistry showed that the PPP2R3A protein was mainly expressed in the cytoplasm of HCC cells. Compared to corresponding peritumoral tissues, expression was higher in HCC tissues (P ≤ 0.001). Correlation analysis showed that high PPP2R3A expression was correlated with preoperative serum alpha-fetoprotein (AFP) levels (P = 0.003), tumor-node-metastasis-t stage (P ≤ 0.001), and envelope invasion (P = 0.001). Univariate analysis showed that overall survival (P ≤ 0.001) and recurrence-free survival (P = 0.025) of patients with high PPP2R3A expression (≥ 4 points) were poor compared to those with low expression (< 4 points). The overall survival rates or recurrence-free survival rates at 1, 2, and 3 years with high PPP2R3A expression were 73%, 38%, and 23% or 31%, 23%, and 23%, respectively. Multivariate analysis showed that high PPP2R3A expression (hazard ratio = 2.900, 95% confidence interval: 1.411-5.960, P = 0.004) was an independent survival risk factor of HCC patients after LT, and it was also an independent predictor of postoperative tumor recurrence. This study also showed in patients with AFP ≥ 400 ng/mL, the overall survival (P ≤ 0.001) and recurrence-free survival (P = 0.023) of those with high PPP2R3A expression were significantly worse compared to those with low PPP2R3A expression. When PPP2R3A expression was low, the overall survival rate (P = 0.461) or recurrence-free survival rate (P = 0.072) after LT in patients with AFP < 400 ng/mL and ≥ 400 ng/mL was not significantly difference. The 1, 2, and 3 year survival rate of patients with low PPP2R3A expression and AFP < 400 ng/mL were 98%, 80%, and 69%, respectively, while patients who met Hangzhou criteria had a post-transplant 1, 2, and 3 years overall survival rate of 89%, 66%, and 55%, respectively. CONCLUSION: High expression of PPP2R3A might be a potential marker for predicting poor prognosis of HCC after LT. Combined with serum AFP levels, PPP2R3A might enhance the accuracy of predicting HCC outcome in patients after LT and supplement the efficacy of the Hangzhou criteria.

Identification and monitoring of fentanyls-related substances in east China sewage water samples by LC-MS for drug enforcement.

Fentanyls abuse is a persistent international concern. New fentanyl derivatives are constantly appearing, circumventing national and international laws. In this study, laboratory degradation experiment with different conditions such as pH, light, temperature and oxygen availability were compared to improve the understanding of the fentanyls degradation pathways. Twelve major degradants of sufentanil and alfentanil were detected and identified together using UHPLC-QTOF-MS. A total of thirty nine fentanyls including twelve typical fentanyl new psychoactive substances, eighteen manufacturing process-related substances and nine key degradants of sufentanil and alfentanil were screened in 120 sewage water samples collected from 20 sewage water treatment plants chosen among 6 urban cities in east China from July to August in 2020 using a validated UHPLC-MS/MS method. Three fentanyls (fentanyl, sufentanil, alfentanil), seven degradants and six manufacturing process-related substances were found in the test samples. The study could provide a useful tool for the monitoring of the abuses, illegal manufacturing or pharmaceuticals related pollutions of fentanyls and their analogs.

Sex-Specific Influence of the SCARB1 Rs5888 SNP on the Serum Lipid Response to Atorvastatin in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Epidemiological studies have shown that there are sex differences in blood lipid levels and lipid responses to statins. Previous studies have shown that the rs5888 single nucleotide polymorphism (SNP) in the scavenger receptor class B type 1 (SCARB1) gene is associated with serum lipid levels in a sex-specific manner. The present study was undertaken to detect the sex-specific influence of the SCARB1 rs5888 SNP on the serum lipid response to atorvastatin in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). METHODS: A total of 158 unrelated ACS patients (108 males, 50 females) were enrolled, and all patients received atorvastatin 20 mg/daily after PCI. Genotyping of the rs5888 SNP was performed by polymerase chain reaction and direct sequencing. Serum lipid profiles were determined before treatment and after an average follow-up time of one year. RESULTS: The baseline serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (Apo)AI levels were higher in females than in males (P<0.05). After treatment with atorvastatin, serum TC, LDL-C, and ApoB were decreased, and ApoAI was increased (P<0.05). The effects of atorvastatin on serum lipid levels were different between males and females, and females had greater decreases in TC, LDL-C and ApoB levels than males (P<0.05). The genotypic frequencies of the rs5888 SNP were not different between males and females. The atorvastatin response was not associated with the rs5888 SNP in males (P > 0.05). Nonetheless, in female individuals carrying the rs5888 T-allele, we observed a greater reduction in TC, LDL-C, and ApoB levels after the use of 20 mg/day atorvastatin (P<0.05). CONCLUSION: This study indicates that the SCARB1 rs5888 T-allele was associated with a greater reduction in serum TC, LDL-C, and ApoB after atorvastatin treatment in female patients with ACS undergoing PCI.

Impurity profiling of alfentanil hydrochloride by liquid chromatography/quadrupole time-of-flight high-resolution mass spectrometric techniques for drug enforcement.

RATIONALE: Fentanyl and its analogues play important roles in the hospital and clinic setting as anesthetics. However, illicitly manufactured fentanyl as well as the new psychoactive substances (NPS) account for 30% of all deaths in the United States. Since fentanyl derivatives and NPS are designed to produce similar effects, their related substances are similar or even have the same active groups. A comprehensive analysis of the related substances of alfentanil hydrochloride can provide a basis for the identification and supervision of fentanyl derivatives and NPS. METHODS: A liquid chromatography/quadrupole time-of-flight tandem mass spectrometry (LC/QTOF-MS/MS) method was developed for the separation and characterization of related substances in alfentanil hydrochloride. Degradation studies were conducted according to the ICH-prescribed stress conditions. The compounds were identified mainly through positive electrospray ionization QTOF high-resolution mass spectrometric measurements of the accurate masses of the precursor and product ions and their calculated elemental compositions. Their formation mechanisms were also discussed. RESULTS: Seventeen related substances were detected in alfentanil hydrochloride and its stressed samples. Among them, nine were process-related substances and the other eight were degradation products. The stress study results demonstrated that alfentanil hydrochloride was unstable under acid, alkaline, and oxidative stress conditions, while relatively stable under dry photolytic and thermal stress conditions. Alfentanil hydrochloride was most susceptible for degradation at the N-phenylpropanamide and piperidine sites. CONCLUSIONS: Process-related alfentanil hydrochloride compounds are useful for determination of synthetic routes and entangling of fentanyl analogues. The stress study results can provide a sound scientific basis for the waste water monitoring of alfentanil. These results are important for routine quality control in the manufacturing and storage of alfentanil hydrochloride, as well as for drug enforcement of fentanyl and its analogues.

Electrocardiographic findings of Wellens syndrome due to coronary artery-pulmonary artery fistula.

A coronary artery fistula (CAF) is an abnormal connection between a coronary artery and any of the four cardiac chambers, the large vessels, or other vascular structures. Wellens syndrome is an ST-segment elevation myocardial infarction equivalent. Although both Wellens syndrome and CAFs have been reported in the literature, they have rarely been reported in the same patient. We herein report a case clinically diagnosed as Wellens syndrome by electrocardiography (ECG) findings; coronary angiography subsequently showed a fistula originating from the left anterior descending artery and draining into the pulmonary artery. The ECG findings then returned to normal after the fistula had been closed by controlled-release coils. These events confirmed that the abnormal ECG findings of Wellens syndrome were due to the CAF.

Changes in Homocysteine Levels Affect Serum Lipid Response to Atorvastatin in Patients With Acute Coronary Syndrome: A Retrospective Observational Study.

OBJECTIVE: The present study investigated whether changes in serum homocysteine (Hcy) levels modify the effects of atorvastatin treatment on blood lipid parameters in patients with acute coronary syndrome (ACS). METHODS: A total of 159 patients with ACS who received regular, long-term treatment with 20 mg/d atorvastatin were included. Depending on the changes in Hcy parameters, they were divided into Hcy reduction (HR) and Hcy elevation (HE) groups. RESULTS: After long-term atorvastatin treatment, total cholesterol (TC), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) B, and Hcy levels were decreased (P < .05), and the ApoAI level was increased (P < .01). Correlation and stratified analysis showed that Hcy or hyperhomocysteinemia was correlated with blood lipids. In both the HE and HR groups, the TC, LDL-C, and ApoB levels after treatment were lower than those before treatment (P < .01), and the ApoAI level was increased compared with that before treatment (P < .05). There was no difference in the reduction of TC, LDL-C, and ApoB levels or in the increase of ApoAI level (P interaction > .05) between the 2 groups. However, there was a clear opposite trend of the effect of atorvastatin on TG and high-density lipoprotein cholesterol (HDL-C) levels between the HR and HE groups (P interaction < .05). In the HR group, the HDL-C level was increased (P < .05), and TGs were decreased compared with those before treatment (P < .01). Nevertheless, in the HE group, the HDL-C level was decreased (P < .05), and TGs (P < .05) were increased compared with those before treatment. CONCLUSION: The effects of atorvastatin on TGs and HDL-C depend on changes in Hcy levels. Patients with a reduced Hcy level after atorvastatin treatment had more favorable lipid parameters.

MADD-FOLH1 Polymorphisms and Their Haplotypes with Serum Lipid Levels and the Risk of Coronary Heart Disease and Ischemic Stroke in a Chinese Han Population.

This study aimed to detect the association of the MADD-FOLH1 single nucleotide polymorphisms (SNPs) and their haplotypes with the risk of coronary heart disease (CHD) and ischemic stroke (IS) in a Chinese Han population. Six SNPs of rs7395662, rs326214, rs326217, rs1051006, rs3736101, and rs7120118 were genotyped in 584 CHD and 555 IS patients, and 596 healthy controls. The genotypic and allelic frequencies of the rs7395662 SNP were different between controls and patients, and the genotypes of the rs7395662 SNP were associated with the risk of CHD and IS in different genetic models. Six main haplotypes among the rs1051006, rs326214, rs326217, rs3736101, and rs7120118 SNPs were detected in our study population, the haplotypes of G-G-T-G-C and G-A-T-G-T were associated with an increased risk of CHD and IS, respectively. The subjects with rs7395662GG genotype in controls had higher triglyceride (TG) and lower high-density lipoprotein cholesterol (HDL-C) levels than the subjects with AA/AG genotypes. Several SNPs interacted with alcohol consumption to influence serum TG (rs326214, rs326217, and rs7120118) and HDL-C (rs7395662) levels. The SNP of rs3736101 interacted with cigarette smoking to modify serum HDL-C levels. The SNP of rs1051006 interacted with body mass index ≥24 kg/m² to modulate serum low-density lipoprotein cholesterol levels. The interactions of several haplotypes and alcohol consumption on the risk of CHD and IS were also observed.

Association of two polymorphisms in the FADS1/FADS2 gene cluster and the risk of coronary artery disease and ischemic stroke.

Little is known about the association of the FADS1/FADS2 SNPs and serum lipid levels and the risk of coronary artery disease (CAD) and ischemic stroke (IS) in the Chinese southern population. The present study aimed to determine such association in the Chinese southern population. A total of 1,669 unrelated subjects (CAD, 534; IS, 553; and healthy controls, 582) were recruited in the study. Genotypes of the FADS1 rs174546 SNP and the FADS2 rs174601 SNP were determined by the SNaPshot Multiplex Kit. The T allele and TT genotype frequencies of the two SNPs were predominant in our study population. The T alleles were associated with increased risk of CAD and IS. Correspondingly, the C alleles were associated with reduced risk of CAD and IS. Haplotype analyses showed that the haplotype of T-T (rs174546-rs174601) was associated with an increased risk for IS, and the haplotype of C-C (rs174546-rs174601) was associated with a reduced risk for CAD and IS. The two SNPs were likely to influence serum lipid levels. The T allele carriers of the two SNPs and rs174601 TT genotype were associated with decreased serum HDL-C and ApoAI levels in the patient groups and with an increased risk of CAD and IS. The present study suggests that the FADS1 rs174546 SNP and the FADS2 rs174601 SNP are associated with the risk of CAD and IS, and are likely to influence serum lipid levels. However, further functional studies are needed to clarify how the two SNPs actually affect serum lipid levels and the risk of CAD and IS.

Association between the MLX interacting protein-like, BUD13 homolog and zinc finger protein 259 gene polymorphisms and serum lipid levels.

This study aimed to detect the association between the MLX interacting protein-like (MLXIPL), BUD13 homolog (BUD13) and zinc finger protein 259 (ZNF259) single nucleotide polymorphisms (SNPs) and serum lipid levels in the Chinese Mulao and Han populations. Genotyping of 9 SNPs was performed in 825 Mulao and 781 Han participants. The genotype and allele frequencies of ZNF259 rs2075290 and rs964184, and BUD13 rs10790162 SNPs were different between the Mulao and Han populations (P < 0.001). The SNPs of ZNF259 rs2075290 and BUD13 rs10790162 were associated with serum total cholesterol levels; ZNF259 rs2075290 and rs964184, BUD13 rs10790162, and MLXIPL rs3812316 and rs13235543 were associated with triglyceride (TG); and MLXIPL rs35332062 was associated with apolipoprotein (Apo) A1 in the Mulaos (P < 0.006-0.001). However, in the Hans, the SNPs of ZNF259 rs2075290 and BUD13 rs10790162 were associated with serum TG levels; ZNF259 rs2075290 was associated with low-density lipoprotein cholesterol and the ApoA1/ApoB ratio (P < 0.006-0.001). Significant linkage disequilibria were noted among ZNF259 rs2075290 and rs964184 and BUD13 rs10790162, and between MLXIPL rs3812316 and rs13235543 (r(2) > 0.05, P < 0.001). The haplotypes of A-C-G-A-C (rs2075290A-rs964184C-rs10790162G-rs17119975A-rs11556024C) and C-C-C-C (rs799161C-rs35332062C-rs3812316C-rs13235543C) accounted for over half of the % haplotype of each ethnic group.

Association of the variants in the BUD13-ZNF259 genes and the risk of hyperlipidaemia.

The single nucleotide polymorphisms (SNPs) in the BUD13 homolog (BUD13) and zinc finger protein 259 (ZNF259) genes have been associated with one or more serum lipid traits in the European populations. However, little is known about such association in the Chinese populations. Our objectives were to determine the association of the BUD13/ZNF259 SNPs and their haplotypes with hypercholesterolaemia (HCH)/hypertriglyceridaemia (HTG) and to identify the possible gene-gene interactions among these SNPs. Genotyping of 6 SNPs was performed in 634 hyperlipidaemic and 547 normolipidaemic participants. The ZNF259 rs2075290, ZNF259 rs964184 and BUD13 rs10790162 SNPs were significantly associated with serum lipid levels in both HCH and non-HCH populations (P < 0.008-0.001). On single locus analysis, only BUD13 rs10790162 was associated with HCH (OR: 2.23, 95% CI: 1.05, 4.75, P = 0.015). The G-G-A-A-C-C haplotype, carrying rs964184-G-allele, was associated with increased risk of HCH (OR: 1.35, 95% CI: 1.10, 1.66, P = 0.005) and HTG (OR: 1.75, 95% CI: 1.39, 2.21, P = 0.000). The A-C-G-G-C-C and A-C-A-G-T-C haplotypes, carrying rs964184-C-allele, were associated with reduced risk of HCH (OR: 0.77, 95% CI: 0.61, 0.99, P = 0.039 and OR: 0.66, 95% CI: 0.47, 0.94, P = 0.021 respectively). On multifactor dimensionality reduction analyses, the two- to three-locus models showed a significant association with HCH and HTG (P < 0.01-0.001). The BUD13/ZNF259 SNPs, which were significant in the European populations, are also replicable in the Southern Chinese population. Moreover, inter-locus interactions may exist among these SNPs. However, further functional studies are required to clarify how these SNPs and genes actually affect the serum lipid levels.

Sex-specific association of the zinc finger protein 259 rs2075290 polymorphism and serum lipid levels.

BACKGROUND: Little is known about the association of ZNF259 rs2075290 single nucleotide polymorphism (SNP) and serum lipid levels in the Chinese population. This study aimed to detect the association of ZNF259 rs2075290 SNP and environmental factors with serum lipid levels between males and females in the Mulao and Han populations. METHODS AND RESULTS: Genotyping of ZNF259 rs2075290 SNP was performed in 788 of Mulao and 778 of Han participants using polymerase chain reaction and restriction fragment length polymorphism. The genotype frequencies were significantly different between Mulao and Han populations (AA, 50.1% Vs 58.9%; AG, 42.3% Vs 35.7%; GG, 7.6% Vs 5.4%, P = 0.002) and between Han males and females (AA, 64.5% Vs 55.2%; AG, 28.3% Vs 40.6%; GG, 7.2% Vs 4.2%, P = 0.001). Serum levels of triglyceride (TG) in Mulao males, and total cholesterol (TC), TG and low-density lipoprotein cholesterol (LDL-C) in Mulao females were different between the AA and AG/GG genotypes (P < 0.05-0.001). Serum TC, LDL-C and apolipoprotein (Apo) A1 levels in Han males, and TG and ApoB levels and ApoA1/ApoB ratio in Han females were different between the AA and AG/GG genotypes (P < 0.05-0.001). An interaction between ZNF259 rs2075290 polymorphism and male gender on serum TC, LDL-C, and ApoA1 levels was noted in Han population (P < 0.05-0.01) but not in Mulao's. CONCLUSIONS: The subjects with AG/GG genotype in Mulao males and females and Han females have less favorable lipid profiles than those with AA genotype. In contrast, the subjects with AG/GG genotype in Han males have more favorable lipid profiles than those with AA genotype. These findings suggest that the association between ZNF259 rs2075290 SNP and serum lipid levels might have ethnic- and/or sex-specificity.

Phosphodiesterase 3A rs7134375 single nucleotide polymorphism and serum lipid levels.

The association between the phosphodiesterase 3A (PDE3A) rs7134375 single nucleotide polymorphism (SNP) and serum lipid levels are not well understood in the general population. The present study was performed in order to detect the association between the rs7134375 SNP and serum lipid levels in the Guangxi Mulao and Han populations. The genotypes of the PDE3A rs7134375 SNP in 761 subjects of the Mulao population and 774 subjects of the Han Chinese population were determined by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. It was observed that serum low-density lipoprotein cholesterol and apolipoprotein B levels were higher in the Mulao population than in the Han population (P<0.05 for each). The frequencies of the C and A alleles were 72.14 and 27.86% in the Mulao population, and 78.55 and 21.45% in the Han population (P<0.01), respectively. The frequencies of the CC, CA and AA genotypes were 52.04, 40.21 and 7.75% in the Mulao population, and 61.50, 34.11 and 4.39% in the Han population (P<0.01), respectively. The frequencies of the C and A alleles were 74.89 and 25.11% in Mulao females, and 68.08 and 31.92% in Mulao males (P<0.01), respectively. The serum triglyceride (TG) levels were different among the genotypes in the Mulao population; however, not in the Han population (P<0.01), and the A allele carriers exhibited lower TG levels than the A allele noncarriers. The serum lipid parameters were also correlated with several environmental factors in the two ethnic groups (P<0.05-0.001). It was concluded that the genotypic and allelic frequencies of the rs7134375 SNP are different between the Mulao and Han populations. In addition, the PDE3A rs7134375 SNP is associated with serum TG levels in the Mulao population, however, not in the Han population.

Association between single nucleotide polymorphism rs1044925 and the risk of coronary artery disease and ischemic stroke.

The present study was performed to clarify the association between the acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) single nucleotide polymorphism (SNP) rs1044925 and the risk of coronary artery disease (CAD) and ischemic stroke (IS) in the Guangxi Han population. Polymerase chain reaction and restriction fragment length polymorphism was performed to determine the genotypes of the ACAT-1 SNP rs1044925 in 1730 unrelated subjects (CAD, 587; IS, 555; and healthy controls; 588). The genotypic and allelic frequencies of rs1044925 were significantly different between the CAD patients and controls (p = 0.015) and borderline different between the IS patients and controls (p = 0.05). The AC/CC genotypes and C allele were associated with a decreased risk of CAD and IS (CAD: p = 0.014 for AC/CC vs. AA, p = 0.022 for C vs. A; IS: p = 0.014 for AC/CC vs. AA; p = 0.017 for C vs. A). The AC/CC genotypes in the healthy controls, but not in CAD or IS patients, were associated with an increased serum high-density lipoprotein cholesterol (HDL-C) concentration. The present study shows that the C allele carriers of ACAT-1 rs1044925 were associated with an increased serum HDL-C level in the healthy controls and decreased risk in CAD and IS patients.

Association of the KLF14 rs4731702 SNP and serum lipid levels in the Guangxi Mulao and Han populations.

The objective of the present study was to detect the association of the rs4731702 single nucleotide polymorphism (SNP) and serum lipid levels in the Guangxi Mulao and Han populations. A total of 727 subjects of Mulao and 740 subjects of Han Chinese were included. Serum low-density lipoprotein cholesterol (LDL-C) and apolipoprotein (Apo) B levels were higher in Mulao than in Han (P < 0.05). The T allele carriers had higher serum LDL-C and ApoAI levels in Mulao, whereas they had lower high-density lipoprotein cholesterol (HDL-C) levels and ratio of ApoAI to ApoB in Han (P < 0.05) than the T allele noncarriers. Subgroup analyses showed that the T allele carriers had higher HDL-C, LDL-C, and ApoAI levels in Mulao males and lower ApoAI levels and ratio of ApoAI to ApoB in Han males than the T allele noncarriers. The subjects with TT genotype in Han females also had higher total cholesterol, LDL-C, ApoAI, and ApoB levels than the subjects with CT or CC genotype. Serum lipid parameters were also correlated with several environmental factors in both ethnic groups. The differences in the association of KLF14 rs4731702 SNP and serum lipid levels between the two ethnic groups might partly result from different gene-environmental interactions.

Scavenger receptor class B type 1 gene rs5888 single nucleotide polymorphism and the risk of coronary artery disease and ischemic stroke: a case-control study.

BACKGROUND: Our previous studies have showed that the rs5888 single nucleotide polymorphism (SNP) in Scavenger receptor class B type 1 (SCARB1) gene is associated with serum lipid levels in the general Chinese populations. The present study was undertaken to detect the associations between rs5888 SNP and the risk of coronary artery disease (CAD) and ischemic stroke (IS). METHODS: A total of 1,716 unrelated subjects (CAD, 601; IS, 533; and healthy controls, 582) were included in this study. Genotyping of the rs5888 SNP were determined by polymerase chain reaction and restriction fragment length polymorphism. RESULTS: The genotypic frequencies of SCARB1 rs5888 SNP were different between CAD patients and controls, the subjects with TT genotype had high risk of CAD (OR = 1.76, P = 0.038 for TT vs. CC; and OR = 1.75, P = 0.036 for TT vs. CC/CT). There was no significant association between genotypes and the risk of IS. Further analysis showed that the subjects with TT genotype in the total population had lower levels of high-density lipoprotein cholesterol than the subjects with CC/CT genotypes (P < 0.05), the subjects with TT genotype in controls but not in CAD or IS patients had higher levels of serum LDL-C and ApoB than those with CC genotype (P < 0.05 for each). CONCLUSIONS: The present study suggests that the SCARB1 rs5888 SNP influences serum lipid levels, and is associated with the risk of CAD.

Interactions of several single nucleotide polymorphisms and high body mass index on serum lipid traits.

The interactions between single nucleotide polymorphisms (SNPs) and high body mass index (BMI) on serum lipid profiles are limited. This study was undertaken to detect the interactions of 10 SNPs and high BMI on serum lipid traits in an isolated population. A total of 978 normal BMI (< 24 kg/m2) and 751 high BMI (≥ 24 kg/m2) subjects of Bai Ku Yao were randomly selected from our previous stratified randomized cluster samples. Genotypes of rs2066715, rs1044925, low density lipoprotein receptor (LDL-R) Ava||, rs2070895, rs2000813, rs1801133, rs3757354, rs505151, rs2016520, and rs5888 SNPs were determined by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. The interactions were detected by factorial design covariance analysis. The genotypic and allelic frequencies of rs2070895 and rs505151 were different between normal and high BMI subjects, the genotypic frequency of rs2000813 and allelic frequency of rs3757354 were also different between normal and high BMI subjects (P < 0.01). The levels of total cholesterol (TC), apolipoprotein (Apo) A1 (rs2066715); TC, low-density lipoprotein cholesterol (LDL-C), ApoA1, ApoB, and ApoA1/ApoB (rs2070895); triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and ApoA1 (rs2000813); TC, HDL-C, LDL-C, ApoA1, and ApoB (rs1801133); HDL-C and ApoA1 (rs3757354) in normal BMI subjects were different among the genotypes (P < 0.01). The levels of LDL-C, ApoB, and ApoA1/ApoB (rs2066715); HDL-C, ApoA1, ApoB, and ApoA1/ApoB (rs2070895); TC, HDL-C, ApoA1, and ApoB (rs2000813); TC, TG, HDL-C, LDL-C, ApoA1, and ApoB (rs1801133); TC, TG, and ApoB (rs3757354); TG (rs505151); TG and ApoA1 and ApoB (rs2016520); and TC, HDL-C, LDL-C, ApoA1, and ApoB (rs5888) in high BMI subjects were also different among the genotypes (P < 0.01). The SNPs of rs2066715 (LDL-C and ApoA1/ApoB); rs2070895 (TC, LDL-C, ApoA1, and ApoB); rs2000813 (ApoB); rs1801133 (TC, TG, and LDL-C); rs3757354 (TC and TG); rs505151 (TG, HDL-C, ApoB, and ApoA1/ApoB); rs2016520 (TG and ApoA1/ApoB); and rs5888 (TG, ApoA1, and ApoB) interacted with high BMI to influence serum lipid levels (P < 0.01). The differences in serum lipid levels between normal and high BMI subjects might partly result from different interactions of several SNPs and high BMI.

Proprotein convertase subtilisin/kexin type 9 gene E670G polymorphism interacts with alcohol consumption to modulate serum lipid levels.

BACKGROUND: Both alcohol consumption and the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene polymorphism modulate serum lipid levels, but their interactions on serum lipid profiles are still unknown. The present study was undertaken to detect the interactions of PCSK9 E670G polymorphism and alcohol consumption on serum lipid levels. METHODS: Genotypes of the PCSK9 E670G in 1352 unrelated subjects (785 non-drinkers and 567 drinkers) were determined by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. The interactions between PCSK9 E670G genotypes and alcohol consumption on serum lipid parameters were detected by using a factorial design covariance analysis after controlling for potential confounders. RESULTS: The levels of serum triglyceride, high-density lipoprotein cholesterol, apolipoprotein (Apo) A1, and the ratio of ApoA1 to ApoB were higher in drinkers than in non-drinkers (P < 0.01 for all), whereas the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and ApoB were lower in drinkers than in non-drinkers (P < 0.001 for all). The genotypic and allelic frequencies of PCSK9 E670G were not different between non-drinkers and drinkers (P > 0.05 for each). The subjects with AA genotype in non-drinkers had higher serum LDL-C levels than the subjects with AG genotype, whereas the subjects with AG genotype in drinkers had higher serum TC levels than the subjects with AA genotypes (P < 0.05 for each). The effects of alcohol consumption on TC and LDL-C levels depended upon genotypes, the subjects with AA genotype had lower serum TC and LDL-C levels in drinkers than in non-drinkers. CONCLUSIONS: Alcohol consumption can modify the effects of the PCSK9 E670G polymorphism on serum TC and LDL-C levels. The subjects with AA genotype of the PCSK9 E670G benefit more from alcohol consumption than the subjects with AG genotype in decreasing serum TC and LDL-C levels.