The novel type II toxin-antitoxin PacTA modulates Pseudomonas aeruginosa iron homeostasis by obstructing the DNA-binding activity of Fur.

Type II toxin-antitoxin (TA) systems are widely distributed in bacterial and archaeal genomes and are involved in diverse critical cellular functions such as defense against phages, biofilm formation, persistence, and virulence. GCN5-related N-acetyltransferase (GNAT) toxin, with an acetyltransferase activity-dependent mechanism of translation inhibition, represents a relatively new and expanding family of type II TA toxins. We here describe a group of GNAT-Xre TA modules widely distributed among Pseudomonas species. We investigated PacTA (one of its members encoded by PA3270/PA3269) from Pseudomonas aeruginosa and demonstrated that the PacT toxin positively regulates iron acquisition in P. aeruginosa. Notably, other than arresting translation through acetylating aminoacyl-tRNAs, PacT can directly bind to Fur, a key ferric uptake regulator, to attenuate its DNA-binding affinity and thus permit the expression of downstream iron-acquisition-related genes. We further showed that the expression of the pacTA locus is upregulated in response to iron starvation and the absence of PacT causes biofilm formation defect, thereby attenuating pathogenesis. Overall, these findings reveal a novel regulatory mechanism of GNAT toxin that controls iron-uptake-related genes and contributes to bacterial virulence.

C Allele of the PPARδ+294T>C Polymorphism Confers a Higher Risk of Hypercholesterolemia, but not Obesity and Insulin Resistance: A Systematic Review and Meta-Analysis.

The relationships of the PPARα Leu162Val and PPARδ+294 T>C polymorphisms with metabolic indexes have been reported to be inconsistent and even contradictory. The meta-analysis was conducted to clarify the relationships between the two variants and the indexes of obesity, insulin resistance, and blood lipids. PubMed, Google Scholar, Embase, and Cochrane Library were searched for eligible studies. Standardized mean difference with 95% confidence interval was calculated to estimate the differences in the metabolic indexes between the genotypes of the Leu162Val and+294 T>C polymorphisms. Heterogeneity among studies was assessed by Cochran's x2-based Q-statistic test. Publication bias was identified by using Begg's test. Forty-one studies (44 585 subjects) and 33 studies (23 018 subjects) were identified in the analyses for the Leu162Val and+294 T>C polymorphisms, respectively. C allele carriers of the+294 T>C polymorphism had significantly higher levels of total cholesterol and low-density lipoprotein cholesterol than TT homozygotes in the whole population. Notably, C allele carriers of the+294 T>C polymorphism had significantly higher levels of triglycerides and total cholesterol in East Asians, but lower levels of triglycerides in West Asians than TT homozygotes. Regarding the Leu162Val polymorphism, it was found that Val allele carriers had significantly higher levels of blood glucose than Leu/Leu homozygotes only in European Caucasians. The meta-analysis demonstrates that C allele of the+294 T>C polymorphism in PPARδ gene confers a higher risk of hypercholesterolemia, which may partly explain the relationship between this variant and coronary artery disease.

The Association between COMT Val158Met Polymorphism and the Post-Traumatic Stress Disorder Risk: A Meta-Analysis.

BACKGROUND: Genetic factors were suggested to have influence on the development of post-traumatic stress disorder (PTSD). The possible association between catechol-O-methyltransferase (COMT) Val158Met polymorphism and PTSD has been evaluated in several studies. But the results were still controversial. Therefore, we conduct this meta-analysis to address these issues. METHODS: The PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched for eligible studies. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to estimate the association between COMT Val158Met polymorphism and PTSD. RESULTS: Five articles including 6 studies with 893 cases and 968 controls were finally included in the present meta-analysis. The pooled analyses did not demonstrate a significant association between the COMT Val158Met polymorphism and PTSD in any of the selected genetic models: allele model (OR = 1.13, 95% CI: 0.97-1.31), dominant model (OR = 1.17, 95% CI: 0.93-1.46), recessive model (OR = 1.44, 95% CI: 0.78-2.66), and additive model (OR = 1.54, 95% CI: 0.85-2.80). Subgroup analyses suggested that the Hardy-Weinberg equilibrium status of genotype distributions could influence the relationship of COMT Val158Met polymorphism and PTSD. CONCLUSIONS: The present meta-analysis suggested that the COMT Val158Met polymorphism may not be associated with the PTSD risk. Further large-scale and population-representative studies are warranted to evaluate the impact of the COMT Val158Met polymorphism on the risk of PTSD.

rs10865710 polymorphism in PPARG promoter is associated with the severity of type 2 diabetes mellitus and coronary artery disease in a Chinese population.

BACKGROUND: Relationship between polymorphisms in peroxisome proliferator-activated receptor gamma (PPARG) and progression of type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) remains to be clarified. METHODS: 635 subjects were divided into T2DM, CAD, T2DM complicated with CAD (T2DM/CAD) and control groups according to diagnostic criteria. The rs10865710 and rs3856806 polymorphisms were genotyped, and the severity of T2DM and CAD was evaluated for all subjects. RESULTS: In patients with T2DM, G allele carriers of rs10865710 polymorphism had significantly higher levels of glucose, triglycerides, apolipoprotein B (ApoB) and lipoprotein (a) (Lp(a)) than non-carriers, T allele carriers of rs3856806 polymorphism had significantly higher levels of glucose, low-density lipoprotein cholesterol (LDL-C), ApoB and Lp(a) than non-carriers. In patients with CAD, G allele carriers of rs10865710 polymorphism had significantly higher levels of total cholesterol (TC), ApoB and Lp(a) than non-carriers, T allele carriers of rs3856806 polymorphism had significantly higher levels of body mass index, blood pressure, TC, LDL-C and ApoB than non-carriers. Patients with one or two G alleles of rs10865710 polymorphism had significantly higher levels of Gensini scores and more diseased coronary branches than those patients without CAD. The rs3856806 polymorphism was not associated with CAD severity, but it was found to be significantly associated with T2DM/CAD, T allele frequency was significantly higher in T2DM/CAD group than that in T2DM/CAD-free group. CONCLUSIONS: The rs10865710 and rs3856806 polymorphisms in PPARG are significantly associated with glucose levels in patients with T2DM. The rs10865710 polymorphism is significantly associated with the severity of CAD, which is possibly mediated by hyperlipidaemia and hyperglycaemia.

Total Glucosides of Paeony Attenuates Ulcerative Colitis via Inhibiting TLR4/NF-κB Signaling Pathway.

The therapeutic effects and mechanisms of action of total glucosides of paeony (TGP) in treating ulcerative colitis remain to be clarified. Mouse model of ulcerative colitis was treated with TGP and the indexes including scores of disease activity index, gross morphologic damage and histological damage, and inflammatory and oxidative stress markers were determined. Patients with ulcerative colitis received TGP capsule therapy and the indexes including efficacy of colonoscopy and histology, scores of Ulcerative Colitis Activity Index (UCAI) and Short Inflammatory Bowel Disease Questionnaire (SIBDQ), and inflammatory parameters were assessed. The expressions of toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) were measured in colonic tissues of mice and patients. TGP treatment significantly increased weight, decreased scores of disease activity index, gross morphologic damage and histological damage, and reduced the levels of tumor necrosis factor-α, interleukin-1ß, malondialdehyde and myeloperoxidase in mouse model. Patients treated with TGP capsule had significantly higher relief rates of diarrhea, abdominal pain, and bloody purulent stool, decreased UCAI and increased SIBDQ scores, and lower levels of erythrocyte sedimentation rate, C-reactive protein and CD4+/CD8+ T-cell ratio than those patients with routine therapy. The overall response rate of TGP capsule was significantly higher than that of routine therapy. TGP treatment significantly suppressed the expressions of TLR4 and NF-κB in colonic tissues of both mouse model and patients with UC. TGP shows a good therapeutic effect on ulcerative colitis in animals and human patients, and the underlying mechanisms may be related to the inhibition of TLR4/NF-κB signaling by TGP.

Associations of the Polymorphisms in ADIPOQ with Circulating Levels of Adiponectin and Lipids: A Meta-Analysis.

The relationships between the rs266729, rs1501299, and rs2241766 polymorphisms in adiponectin gene (ADIPOQ) and circulating levels of adiponectin and lipids remain to be clarified. Databases including PubMed and Embase were searched for eligible studies. The random-effects model was used, and standardized mean difference (SMD) with 95% confidence interval (CI) was calculated to estimate the differences in circulating levels of adiponectin and lipids between the subjects with different genotypes. A total of 12 810, 17 319, and 21 361 subjects were identified in the analyses for the rs266729, rs1501299, and rs2241766 polymorphisms, respectively. G allele carriers of the rs266729 polymorphism had lower levels of adiponectin (SMD=-0.28, 95% CI=-0.43 to-0.12) and high-density lipoprotein cholesterol (HDL-C) (SMD=-0.10, 95% CI=-0.17 to-0.02) than CC homozygotes; T allele carriers of the rs1501299 polymorphism had higher levels of adiponectin (SMD=0.21, 95% CI=0.05 to 0.36) and HDL-C (SMD=0.09, 95% CI=0.04 to 0.15) and lower levels of triglycerides (SMD=-0.06, 95% CI=-0.12 to-0.01) than GG homozygotes; G allele carriers of the rs2241766 polymorphism had lower levels of adiponectin (SMD=-0.18, 95% CI=-0.31 to-0.05) and HDL-C (SMD=-0.12, 95% CI=-0.20 to-0.04) than TT homozygotes. This meta-analysis suggests that the rs266729, rs1501299, and rs2241766 polymorphisms of ADIPOQ are significantly associated with circulating levels of adiponectin and lipids, which may partly explain the associations between these polymorphisms and coronary artery disease.

Sulfation of Quercitrin, Epicatechin and Rutin by Human Cytosolic Sulfotransferases (SULTs): Differential Effects of SULT Genetic Polymorphisms.

Radix Bupleuri is one of the most widely used herbal medicines in China for the treatment of fever, pain, and/or chronic inflammation. Quercitrin, epicatechin, and rutin, the flavonoids present in Radix Bupleuri, have been reported to display anti-inflammatory, antitumor, and antioxidant biological activities among others. Sulfation has been reported to play an important role in the metabolism of flavonoids. In this study, we aimed to systematically identify the human cytosolic sulfotransferase enzymes that are capable of catalyzing the sulfation of quercitrin, epicatechin, and rutin. Of the thirteen known human cytosolic sulfotransferases, three (cytosolic sulfotransferase 1A1, cytosolic sulfotransferase 1C2, and cytosolic sulfotransferase 1C4) displayed sulfating activity toward quercitrin, three (cytosolic sulfotransferase 1A1, cytosolic sulfotransferase 1A3, and cytosolic sulfotransferase 1C4) displayed sulfating activity toward epicatechin, and six (cytosolic sulfotransferase 1A1, cytosolic sulfotransferase 1A2, cytosolic sulfotransferase 1A3, cytosolic sulfotransferase 1B1, cytosolic sulfotransferase 1C4, and cytosolic sulfotransferase 1E1) displayed sulfating activity toward rutin. The kinetic parameters of the cytosolic sulfotransferases that showed the strongest sulfating activities were determined. To investigate the effects of genetic polymorphisms on the sulfation of quercitrin, epicatechin, and rutin, individual panels of cytosolic sulfotransferase allozymes previously prepared were analyzed and shown to display differential sulfating activities toward each of the three flavonoids. Taken together, these results provided a biochemical basis underlying the metabolism of quercitrin, epicatechin, and rutin through sulfation in humans.

Effects of ABCA1 gene polymorphisms on risk factors, susceptibility and severity of coronary artery disease.

BACKGROUND: The relationships between the rs1800976, rs4149313 and rs2230806 polymorphisms in ATP binding cassette protein A1 and severity of coronary artery disease (CAD) remain unclear. METHODS: Four hundred and forty-two patients with CAD and 217 CAD-free subjects were enrolled in this study. The rs1800976, rs4149313 and rs2230806 polymorphisms were genotyped by PCR-RFLP. Severity of CAD was evaluated by Gensini score system, number of stenotic coronary vessels and extent of coronary stenosis. RESULTS: C allele of the rs1800976 polymorphism, G allele of the rs4149313 polymorphism and A allele of the rs2230806 polymorphism were found to be risk alleles for CAD (p<0.05 for all). In patients with CAD, C allele of the rs1800976 polymorphism was associated with high levels of hypersensitive C reactive protein (hs-CRP) and cystatin c (CysC), and its frequency increased with percentiles of Gensini score, number of stenotic coronary vessels and extent of coronary stenosis (p<0.05 for all). The subjects with GA genotype of the rs4149313 polymorphism had higher levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B and hs-CRP than those with AA genotype (p<0.05 for all). The subjects with AA genotype of the rs2230806 polymorphism had higher levels of TC, LDL-C and uric acid than those with GA genotype (p<0.05 for all). No associations between the rs4149313 or rs2230806 polymorphism and severity of CAD were detected. CONCLUSIONS: The rs1800976 polymorphism is significantly associated with the occurrence and severity of CAD, which is possibly mediated by hs-CRP and CysC.

Associations of the NOS3 rs1799983 polymorphism with circulating nitric oxide and lipid levels: a systematic review and meta-analysis.

BACKGROUND: Circulating nitric oxide (NO) and lipid levels are closely associated with coronary artery disease (CAD). It is unclear whether the rs1799983 polymorphism in endothelial nitric oxide synthase (NOS3) gene is associated with plasma levels of NO and lipids. This systematic review and meta-analysis (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) aimed to clarify the relationships between the rs1799983 polymorphism and plasma levels of NO and lipids. METHODS: Sixteen studies (2702 subjects) and 59 studies (14 148 subjects) were identified for the association analyses for NO and lipids, respectively. Mean difference (MD) and 95% CI were used to estimate the effects of the rs1799983 polymorphism on plasma NO and lipid levels. The primary outcome variable was NO, and the secondary outcomes included triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). RESULTS: Carriers of the T allele had lower levels of NO (MD -0.27 µmol/L, 95% CI -0.42 to -0.12 µmol/L, p<0.001) and HDL-C (MD -0.07 mmol/L, 95% CI -0.14 to -0.00 mmol/L, p=0.04), and higher levels of TC (MD 0.13 mmol/L, 95% CI 0.06 to 0.20 mmol/L, p<0.001) and LDL-C (MD 0.14 mmol/L, 95% CI 0.05 to 0.22 mmol/L, p=0.002) than the non-carriers. Triglyceride levels were comparable between the genotypes. CONCLUSION: The association between the NOS3 rs1799983 polymorphism and CAD may be partly mediated by abnormal NO and lipid levels caused by the T allele.

Associations of the PON1 rs854560 polymorphism with plasma lipid levels: a meta-analysis.

BACKGROUND: Previous studies have investigated the associations of paraoxonase 1 (PON1) rs854560 polymorphism with plasma lipid levels, but the results are inconclusive. This meta-analysis aimed to clarify the associations of the rs854560 polymorphism with plasma lipid levels. METHODS: A comprehensive search of the literature was carried out by using the databases which include Medline, Google Scholar, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang and VIP database up till August 2018. The pooled standardized mean difference (SMD) with 95% confidence interval (CI) was used to assess the differences in lipid levels between the genotypes. Begg's funnel plots and Egger's test were used to examine the publication bias. RESULTS: A total of 41 studies (22,844 subjects) were identified for the associations of rs854560 polymorphism with plasma lipid levels. The M carriers had lower levels of high-density lipoprotein Cholesterol (HDL-C) (SMD = - 0.15, 95% CI = - 0.23--0.07, P < 0.01) and apolipoprotein A-I (APOA1) (SMD = - 0.67, 95% CI = - 0.93--0.41, P < 0.01) than the non-carriers. Subgroup analysis by ethnicity revealed that the effect on HDL level was significant in Caucasians and the subjects of other ethnic origins. No publication bias was detected in this meta-analysis. CONCLUSIONS: The meta-analysis suggests that the PON1 rs854560 polymorphism is associated with a lower HDL-C level in Caucasians and subjects of other ethnic origins.

Associations of the MTHFR rs1801133 polymorphism with coronary artery disease and lipid levels: a systematic review and updated meta-analysis.

BACKGROUND: The associations of the 5,10-methylenetetrahydrofolate reductase gene (MTHFR) rs1801133 polymorphism with coronary artery disease (CAD) and plasma lipid levels have been widely investigated, but the results were inconsistent and inconclusive. This meta-analysis aimed to clarify the relationships of the rs1801133 polymorphism with CAD and plasma lipid levels. METHODS: By searching in PubMed, Google Scholar, Web of Science, Cochrane Library, Wanfang, VIP and CNKI databases, 123 studies (87,020 subjects) and 65 studies (85,554 subjects) were identified for the CAD association analysis and the lipid association analysis, respectively. Odds ratio (OR) and standardized mean difference (SMD) were used to determine the effects of the rs1801133 polymorphism on CAD risk and lipid levels, respectively. RESULTS: The variant T allele of the rs1801133 polymorphism was associated with increased risk of CAD under allelic model [OR = 1.11, 95% confidence interval (CI) = 1.06-1.17, P < 0.01], additive model (OR = 1.25, 95% CI = 1.14-1.37, P < 0.01), dominant model (OR = 1.11, 95% CI = 1.04-1.17, P < 0.01), and recessive model (OR = 1.22, 95% CI = 1.12-1.32, P < 0.01). The T carriers had higher levels of total cholesterol (TC) (SMD = 0.04, 95% CI = 0.01-0.07, P = 0.02) and low-density lipoprotein cholesterol (LDL-C) (SMD = 0.07, 95% CI = 0.01-0.12, P = 0.01) than the non-carriers. CONCLUSIONS: The meta-analysis suggested that the T allele of the rs1801133 polymorphism is a risk factor for CAD, which is possibly and partly mediated by abnormal lipid levels.

The lipid-lowering effects of Danhong and Huangqi injections: a meta-analysis of clinical controlled trials.

BACKGROUND: Dyslipidaemia is a major risk factor for coronary heart disease (CHD). Danhong and Huangqi injections, two traditional Chinese medicine prescriptions, have been widely studied regarding their lipid-lowering properties. However, the results were inconsistent and inconclusive. Thus, we conducted this meta-analysis of clinical controlled trials to clarify the lipid-lowering effects of Danhong and Huangqi injections. METHODS: The databases including PubMed, Google Scholar, Web of Science, Cochrane Library, Wanfang Database, CNKI and VIP were searched. The following information was obtained from each study: first author, age, gender, ethnicity, health condition, treatment dose, treatment duration, sample size, mean and standard deviation or standard error of lipid variables before and after treatment. The changes in lipid levels from pre- to post-treatment were calculated and compared between the control groups and the treatment groups in this meta-analysis. RESULTS: Forty-four studies (5021 subjects) and 7 studies (542 subjects) were respectively identified for Danhong and Huangqi injections. Compared with the control groups, Danhong injection yielded a significant reduction in triglycerides (TG) [standardized mean difference (SMD) = - 0.76, 95% confidence interval (CI) = (- 0.91, - 0.61), P <  0.001], total cholesterol (TC) [SMD = - 1.29, 95% CI = (- 1.56, - 1.03), P <  0.001] and low-density lipoprotein cholesterol (LDL-C) [SMD = - 0.76, 95% CI = (- 0.93, - 0.59), P <  0.001], and a significant elevation in high-density lipoprotein cholesterol (HDL-C) [SMD = 0.70, 95% CI = (0.41, 0.98), P <  0.001]. Regarding Huangqi injection, it yielded a significant reduction in TC [SMD = - 1.13, 95% CI = (- 2.09, - 0.16), P = 0.02] and marginally in TG [SMD = - 1.27, 95% CI = (- 2.53, 0.00), P = 0.05] comparing with the control groups. CONCLUSIONS: Danhong injection can effectively decrease the plasma levels of TG, TC and LDL-C, and increase HDL-C levels. Huangqi injection also has significant effects on TG and TC reduction, but not as powerful as Danhong injection.

[Associations of the MicroRNA-143/145 Polymorphisms with Cardiovascular Risk Factors and the Severity of Coronary Heart Disease].

Objective To explore the possible effects of the microRNA(miR)-143/145 polymorphisms on cardiovascular risk factors and the severity of coronary heart disease(CHD) in Chinese Han people. Methods Polymerase chain reaction-restriction fragment length polymorphism analysis was employed to identify the genotypes of the rs353292 and rs4705343 polymorphisms for 380 patients with CHD and 163 CHD-free controls. The physiological and biochemical parameters between the genotypes were compared in the CHD patients and in controls,and the incidence of myocardial infarction(MI) was also compared between the genotypes in the CHD patients. Results The subjects with the rs353292 TT genotype had higher serum levels of triglycerides(F=3.00,P=0.05) and glucose(F=9.91,P<0.001) than the C carriers,and the subjects with the rs4705343 TT genotype had significantly higher prevalence of hypertension(Χ2=6.35,P=0.04) than the C carriers in the control group. The patients with the rs353292 TT genotype had significantly higher serum levels of hypersensitive C-reactive protein(hs-CRP)(F=8.43,P<0.001) than the C carriers in the CHD group,and the frequency of MI was significantly higher in the patients with the rs353292 TT genotype than that in the C carrier patients(Χ2=5.29,P=0.02). Conclusion The T allele of the rs353292 polymorphism is associated with serum hs-CRP levels in CHD patients,and it may affect the occurrence and development of MI by up-regulation of CRP gene through miR-143/145. The rs4705343 polymorphism is not related to the risk and severity of CHD.

Low-Density Lipoprotein Receptor Signaling Mediates the Triglyceride-Lowering Action of Akkermansia muciniphila in Genetic-Induced Hyperlipidemia.

OBJECTIVE: Akkermansia muciniphila (A muciniphila) is a mucin-degrading bacterium that resides in the mucus layer whose abundance inversely correlates with body weight and the development of diabetes mellitus in mice and humans. The objective of this study was to explore the regulatory effect of A muciniphila on host lipoprotein metabolism, insulin sensitivity, and hepatic metabolic inflammation. APPROACH AND RESULTS: By establishing a novel mouse model that colonized the A muciniphila in the gastrointestinal tract of the cAMP-responsive binding protein H (CREBH)-deficient mouse and in vivo chylomicron assay, we found that increased colonization of A muciniphila in the gastrointestinal tract of wild-type mice protected mice from an acute fat load-induced hyperlipidemia compared with vehicle-treated mice. A muciniphila administration also significantly ameliorated chronic hypertriglyceridemia, improved insulin sensitivity, and prevented overproduction of postprandial chylomicrons in CREBH-null mice. Mechanistic studies revealed that increased A muciniphila colonization induced expression of low-density lipoprotein receptors and apolipoprotein E in the hepatocytes of CREBH-null mice, which facilitated the uptake of intermediate-density lipoprotein via the mediation of apolipoprotein B100 and apolipoprotein E, leading to the increased clearance of triglyceride-rich lipoprotein remnants, chylomicron remnants, and intermediate-density lipoproteins, from the circulation. Treatment with A muciniphila further improved hepatic endoplasmic reticulum stress and metabolic inflammation in CREBH-null mice. CONCLUSIONS: Increased colonization of the disease-protective gut bacteria A muciniphila protected the host from acute and chronic hyperlipidemia by enhancing the low-density lipoprotein receptor expression and alleviating hepatic endoplasmic reticulum stress and the inflammatory response in CREBH-null mice.

Associations of the APOB rs693 and rs17240441 polymorphisms with plasma APOB and lipid levels: a meta-analysis.

BACKGROUND: The associations of the apolipoprotein B gene (APOB) rs693 and rs17240441 polymorphisms with plasma levels of APOB and lipids have been widely explored, but the results were inconclusive. This meta-analysis aimed to clarify the associations of the rs693 and rs17240441 polymorphisms with fasting APOB and lipid levels. METHODS: Sixty-one studies (50,018 subjects) and 23 studies (8425 subjects) were respectively identified for the rs693 and rs17240441 polymorphisms by searching in PubMed, Google Scholar, Web of Science, Cochrane Library, Wanfang, VIP and CNKI databases. The following information was collected for each study: first author, age, gender, ethnicity, health condition, sample size, genotyping, lipid assay method, mean and standard deviation or standard error of APOB and lipid variables by genotypes. A dominant model was used for this meta-analysis. RESULTS: The carriers of the rs693 variant allele (T) had higher levels of APOB [standardized mean difference (SMD) = 0.26, 95% confidence interval (CI) = 0.16-0.36, P < 0.01], triglycerides (TG) (SMD = 0.12, 95% CI = 0.05-0.20, P < 0.01), total cholesterol (TC) (SMD = 0.24, 95% CI = 0.17-0.30, P < 0.01) and low-density lipoprotein cholesterol (LDL-C) (SMD = 0.22, 95% CI = 0.14-0.30, P < 0.01), and lower levels of high-density lipoprotein cholesterol (HDL-C) (SMD = -0.06, 95% CI = -0.11-0.01, P = 0.01) than the non-carriers. The carriers of the rs17240441 deletion allele had higher levels of APOB (SMD = 0.13, 95% CI = 0.06-0.20, P < 0.01), TC (SMD = 0.17, 95% CI = 0.07-0.26, P < 0.01) and LDL-C (SMD = 0.15, 95% CI = 0.07-0.23, P < 0.01) than the non-carriers. CONCLUSIONS: The rs693 polymorphism is significantly associated with higher levels of APOB, TG, TC and LDL-C, and lower levels of HDL-C. The rs17240441 polymorphism is significantly associated with higher levels of APOB, TC and LDL-C. Further studies are needed to elucidate the underlying mechanisms.

The APOA5 rs662799 polymorphism is associated with dyslipidemia and the severity of coronary heart disease in Chinese women.

BACKGROUND: The APOA5 rs662799 polymorphism has been widely reported regarding its associations with the plasma lipid levels and the occurrence of coronary heart disease (CHD), whereas its relationship with the severity of CHD has not yet been explored. METHODS: Four hundred and seventy-eight angiografically defined subjects (325 CHD patients and 153 CHD-free controls) were enrolled in this study. The rs662799 polymorphism was genotyped, and the fasting lipid data were collected for all participants. The severity of CHD was evaluated for the CHD patients by using Gensini scores. RESULTS: The variant C allele of the rs662799 polymorphism was associated with lower levels of HDL-C in CHD-free women, and higher levels of TG and TG/HDL-C in women with CHD (P < 0.05 for all). The C allele was associated with higher prevalence of dyslipidemia and higher levels of Gensini scores only in women (P < 0.05 for both), but not in men. Multivariate linear regression analysis showed that the rs662799 polymorphism was independently associated with the Gensini scores in women after adjustment for other potential CHD risk factors (Beta = 0.157, 95 % CI: 0.017-0.298, P = 0.028). CONCLUSION: Our data indicate that the rs662799 polymorphism is associated with dyslipidemia and the severity of CHD in Chinese women.

Associations of the APOC3 rs5128 polymorphism with plasma APOC3 and lipid levels: a meta-analysis.

BACKGROUND: Studies of the association between the apolipoprotein C3 gene (APOC3) rs5128 polymorphism and plasma levels of apolipoprotein C3 (APOC3) and lipids have reported apparently conflicting findings. This meta-analysis aimed to investigate the associations of the rs5128 polymorphism with fasting APOC3 and lipid levels. METHODS: The following information was abstracted for each study: ethnicity, age, sex, health condition, sample size, genotyping and lipid assay methods, mean and standard deviation or standard error by genotypes for APOC3 and lipid variables. There were 42 eligible studies with 23846 subjects included in this meta-analysis. A dominant model was used for this meta-analysis. RESULTS: The results showed that the carriers of the variant allele G had higher levels of APOC3 [standardized mean difference (SMD): 0.22, 95% confidence interval (CI): 0.12-0.31, P<0.00001], triglycerides (TG) (SMD: 0.33, 95% CI: 0.23-0.44, P<0.00001), total cholesterol (TC) (SMD: 0.15, 95% CI: 0.09-0.22, P<0.00001), and low-density lipoprotein cholesterol (LDL-C) (SMD: 0.11, 95% CI: 0.04-0.17, P=0.001) than the non-carriers. No significant association between the APOC3 rs5128 polymorphism and lower levels of high-density lipoprotein cholesterol (HDL-C) was detected under the dominant model (SMD: -0.03, 95% CI: -0.06-0.01, P=0.156). CONCLUSIONS: The results from the present meta-analysis demonstrate a significant association between the APOC3 rs5128 polymorphism and higher levels of APOC3, TG, TC and LDL-C, but further studies are needed to elucidate the underlying mechanisms.

The apoB100/apoAI ratio is independently associated with the severity of coronary heart disease: a cross sectional study in patients undergoing coronary angiography.

BACKGROUND: Lipoprotein ratios have been shown to be associated with the occurrence of coronary heart disease (CHD), but little is known about their relationships with the severity of CHD. METHODS: A total of 792 angiographically defined CHD patients were enrolled following their admission. Patients were stratified into three groups based on the tertile of the Gensini scores (≤33(rd) percentile, 33(rd) to 66(th) percentile and ≥66(th) percentile) or the number of stenotic coronary branches (single-branch stenosis, double-branch stenosis and multi-branch stenosis). Demographic and biochemical data were collected and lipoprotein ratios were calculated. Logistic regression and path analysis were employed to examine the relationships between the lipoprotein ratios and the severity of CHD. RESULTS: The ratios of low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) and apolipoprotein B100 (apoB100)/apolipoprotein AI (apoAI) increased with the tertile of the Gensini scores (P < 0.05 for both). The ratios of triglyceride (TG)/HDL-C, total cholesterol (TC)/HDL-C, LDL-C/HDL-C and apoB100/apoAI increased with the number of stenotic coronary branches (P < 0.05 for all). The univariate logistic regression showed that the ratios of TC/HDL-C, LDL-C/HDL-C and apoB100/apoAI were positively associated with both the tertile of the Gensini scores and the number of stenotic vessels (P < 0.05 for all), and the ratio of TG/HDL-C was positively associated with the number of stenotic vessels (P < 0.05). In multivariate logistic analysis, only the ratio of apoB100/apoAI was independently and positively associated with the tertile of the Gensini scores (OR = 2.93, 95% CI = 1.17-7.34, P = 0.022) and the number of stenotic vessels (OR = 3.14, 95 % CI = 1.01-6.47, P = 0.048) after adjusting for the possible confounding variables. The apoB100/apoAI ratio was also shown to be a direct mediator between the risk factors including age, BMI, HDL-C, LDL-C, apoB100 and apoAI and the severity of CHD by path analysis. CONCLUSION: Our data indicate that the apoB100/apoAI ratio could be a useful predictor for evaluating the severity of coronary stenosis in CHD patients.

[Advances in the Association between Apolipoprotein (a) Gene Polymorphisms and Coronary Heart Disease].

Human apolipoprotein (a) (LPA) gene is highly polymorphic, and the polymorphic loci on this gene include the Kringle 4 subtype 2(KIV-2) repeat polymorphism, the pentanucleotide repeat (TTTTA)n polymorphism, and a number of single nucleotide polymorphisms. KIV-2 repeat polymorphism was found to be significantly associated with coronary heart disease(CHD), and the reducing number of KIV-2 repeats is a risk factor for CHD. Both the increase and decrease of the pentanucleotide repeat(TTTTA)n polymorphism repeats are possibly associated with CHD risk. In single nucleotide polymorphisms loci, the rs10455872 and rs3798220 loci were widely reported to be associated with CHD, while other loci were less reported. The association between LPA polymorphisms and CHD may be mediated by either the elevation of plasma LPA level or the change of LPA subtypes. This article reviews the association between the LPA polymorphisms and CHD and the underlying mechanisms.