The Association Between <Emphasis Type="Italic">APOA5</Emphasis> Gene Polymorphisms and Plasma Lipids in the Turkish Cypriot Population: A Possible Biomarker for Preventing Cardiovascular Diseases

Apolipoprotein A5 (APOA5 or APO A-V) polymorphisms have long been reported to be associated with cardiovascular disease and plasma lipid levels. The present study was undertaken to investigate the relationship between the rs662799, rs3135507, and rs2075291 with biochemical parameters in the Turkish Cypriot population. A total of 100 Turkish Cypriot volunteer subjects (53 female and 47 male), with a mean age of 40.8, participated in the study. A basic biochemical analysis, including serum glucose, total serum cholesterol, HDL-C, LDL-C, and triglycerides, was performed for each participant. Genotyping for the APOA5 three polymorphisms was performed by polymerase chain reaction followed by restriction fragment length polymorphism analysis. Biochemical parameters except the low-density lipoprotein cholesterol (LDL-C) were all within the normal limits. LDL-C was found to be slightly elevated in participants according to WHO guidelines. With respect to the genotype and allele distributions of APOA5 rs662799 T>C polymorphism, TT genotypes are more frequent (62%) in the population and the frequency of T allele is 0.78. The TT genotype for APOA5 rs2075291 G<T was not observed in the study population. Ancestral GG is the only genotype present in the study population. Minor Allele Frequency of APOA5 rs3135507 G>A variant is 0.12 for the A allele. No association between the two studied APOA5 polymorphisms (rs662799 and rs3135507) and the biochemical components of glucose, total cholesterol, and triglyceride were observed. On the other hand, a strong statistical association between the high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) clinical parameters and APOA5 rs662799 CC and rs3135507 AA genotypes was found (p = 0.014 and p = 0.017, respectively). APOA5 polymorphisms rs662799 and rs3135507, with the CC and the AA genotypes, respectively, are associated with increased levels of both high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) in the Turkish Cypriot population.     

Uncoupling associations of risk alleles with endophenotypes and phenotypes: insights from the ApoB locus and heart‐related traits

Traditionally, genomewide association studies (GWAS) have emphasized the benefits of large samples in the analyses of age‐related traits rather than their specific properties. We adopted a realistic concept of genetic susceptibility to inherently heterogeneous, age‐related traits driven by the elusive role of evolution in their properties. We analyzed in detail the associations of rs693 and rs562338 polymorphisms representing the Apolipoprotein B locus with endophenotypes (total cholesterol [TC] and high‐density lipoprotein cholesterol) and phenotypes (myocardial infarction [MI] and survival) in four large‐scale studies, which include 20 748 individuals with 2357 MI events. We showed that a strong, robust predisposition of rs693 and rs562338 to TC (β = 0.72, P = 7.7 × 10^?30 for rs693 and β = ?1.08, P = 9.8 × 10^?42 for rs562338) is not translated into a predisposition to MI and survival. The rs693_A allele influences risks of MI and mortality after MI additively with lipids. This allele shows antagonistic effects—protecting against MI risks (β = ?0.18, P = 1.1 × 10^?5) or increasing MI risks (β = 0.15, P = 2.8 × 10^?3) and mortality after MI, in different populations. Paradoxically, increased TC concentrations can be protective against MI for the rs693_A allele carriers. Our results uncouple the influences of the same alleles on endophenotypes and phenotypes despite potential causal relationships among the latter. Our strategy reveals virtually genomewide significance for the associations of rs693 with MI (P = 5.5 × 10^?8) that is contrasted with a weak estimate following the traditional, sample‐size‐centered GWAS strategy (P = 0.16) in the same sample. These results caution against the use of the traditional GWAS strategy for gaining profound insights into genetic predisposition to healthspan and lifespan.     

Influence of b2 adrenergic receptor polymorphism (rs1042713 and rs1042714) on anthropometric,hormonal and lipid profiles in polycystic ovarian syndrome

BackgroundPolycystic ovarian syndrome (PCOS) is a frequently encountered disorder. This study aimed to identify polymorphisms in ADRB2 in Saudi PCOS development and to study its influence on lipids, hormones, and anthropometric parameters.MethodsSaudi females (100) suffering from PCOS and healthy controls (100) were investigated. The estimation of cholesterol, triglycerides, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), plasma glucose, leptin Insulin, and ghrelin were carried out. The DNA was extracted, and ADRB2 fragment carrying the exon 1 was amplified and sequenced.ResultsThe waist, W/H ratio, lipids, glucose, and insulin were significantly higher in the obese PCOS compared to the normal weight group. The leptin and ghrelin were not different. Two single nucleotide polymorphisms (SNPs): rs1042713 (Arg16Gly; A>G) and rs1042714 (Gln27Glu; C>G) were identified. The genotype and allele frequency of rs1042713 did not differ in the total PCOS and normal weight, and obese PCOS compare to the controls. However, rs1042714 was significantly associated with PCOS development, where the minor G allele was protective against PCOS development.ConclusionsThe rs1042714 polymorphism of the ADRB associates with PCOS development in Saudis, while rs1042713 does not. However, the GG genotype of rs1042713 associates significantly with elevated BMI, waist, hip, W/H, and leptin, and decreased ghrelin. On the other hand, rs1042714 genotypes do not associate with any abnormality except the homozygous GG have higher triglycerides and lower HDL-C. Interestingly, glucose showed different correlation patterns in individuals carrying different genotypes of the two studied SNP, indicating clearly that the metabolic responses to a normal nutrient are significantly influenced by the genotypes of the SNPs in ADRB2.     

Association of polymorphisms at restriction enzyme recognition sites of apolipoprotein B and E gene with dyslipidemia in children undergoing primary nephrotic syndrome

Background Dyslipidemia, a common complication, is very prevalent in children with primary nephrotic syndrome (PNS). Recent studies have shown that genetic basis may be involved in the onset of HLP secondary to PNS. ApoB and E have been identified as the important candidate genes for lipid abnormalities. Objective: To investigate the association of apolipoprotein B (apoB) and E (apoE) genetic polymorphisms (Xba I, EcoR I, Msp I, and Hha I) with parameters describing the serum lipid profiles in children undergoing PNS. Methods: Genomic DNA was extracted from 250 children diagnosed with PNS and 200 healthy controls with neither allergic nor renal disease. ApoB (Xba I, EcoR I, and Msp I) and apoE (Hha I) genotypes were determined by PCR-restriction fragment length polymorphism (RFLP) analysis. The fasting serum lipoprotein (a) [Lp(a)], total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (apoA1), apoB, and total protein from a 24-h urine sample were measured. Results: No significant differences in genotypes and alleles frequencies were observed for the apoB Xba I, EcoR I, Msp I and the apoE Hha I restriction sites in PNS patients as compared to controls (P > 0.05). Patients and controls with X + allele exhibited significantly higher serum levels of Lp(a), TC, nonHDL-C, LDL-C, LDL-C/HDL-C ratio, and apoB than that with X− allele (P < 0.05), whereas for apoA1/B ratio the opposite was found (P < 0.01). E−/E− carriers had significantly higher Lp(a), TC, HDL-C, and apoA1 concentrations than did E+/E− or E+/E+ carriers in control group (P < 0.05). Healthy children carrying the rare EcoR I allele had higher mean Lp(a), TC, and HDL-C levels than homozygotes for E+ (P < 0.05). Higher Lp(a) serum concentrations were observed in patients with E− allele (P < 0.05). No significant differences in lipid parameters were determined for the apoB Msp I and apoE Hha I the polymorphisms study (P > 0.05). When genetic variations were compared with urinary protein excretion, the Xba I X− allele was more frequent in patients with elevated proteinuria (P < 0.01). Conclusion: Presence of Xba I X+ allele and/or EcoR I E− at the apoB gene may be risk factors for lipid abnormalities secondary to childhood PNS.     

2型糖尿病患者血清Irisin水平与胰岛素抵抗的相关性研究

目的:探讨2型糖尿病患者血清Irision水平和胰岛素抵抗的相关性及其影响因素。方法:2型糖尿病患者50例,纳入健康人群30例为对照组。采用酶联免疫吸附法测定研究对象血清Irisin水平;同时测定糖尿病患者C肽、胰岛素抵抗指数、糖化血红蛋白水平。采用多元回归分析分析影响血清Irisin水平的因子。结果:病例组和对照组间BMI、腰围、血清Irisin、低密度脂蛋白间差异有统计学意义(p0.05)。血清Irisin水平和BMI、腰围、低密度脂蛋白、糖化血红蛋白、胰岛素抵抗指数、糖尿病病程呈负相关(r=-0.73,-0.68,-0.56,-079,-0.65,-0.73,均P0.05)。血清Irisin水平和C肽成正相关(r=0.62,P0.05)。胰岛素抵抗指数、糖尿病病程是影响血清Irisin水平的独立负影响因子。结论:糖尿病患者血清Irisin水平明显降低,和糖尿病患者胰岛素抵抗和病程密切相关。     

Effects of PCSK9 genetic variants on plasma LDL cholesterol levels and risk of premature myocardial infarction in the Italian population

The R46L variant in the proprotein-convertase subtilisin-kexin type 9 (PCSK9) gene was associated with reduced levels of LDL and total cholesterol and with a lower risk of coronary artery disease. We investigated the association of R46L with myocardial infarction (MI) in 1,880 Italian patients with premature MI and 1,880 controls. A trend toward a protective effect of the L46 allele was observed [odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.49–1.13; P = 0.17], although the association with MI was not significant. This is probably due to the combined effect of the low frequency of R46L among Italians and of the young age of the analyzed cohort for whom the impact of coronary atherosclerosis is less important. This hypothesis was indirectly confirmed by the significant association found after including 1,056 additional older controls (OR = 0.67, 95% CI = 0.46-0.97; P = 0.036). LDL cholesterol was significantly lower in L46 carriers (116.2 ± 34.7 mg/dl) than in noncarriers (137.4 ± 47.3 mg/dl; P = 0.00022); a similar reduction was observed for total cholesterol (191.7 ± 37.7 vs. 211.7 ± 49 mg/dl; P = 0.00019). Analysis of 23 additional polymorphisms in the PCSK9 region identified another single nucleotide polymorphism (SNP) (rs11206510) associated with cholesterol levels. We confirmed that the L46 allele not only decreases LDL cholesterol but also protects against MI. Moreover, we replicated the association of total and LDL cholesterol with the SNP rs11206510.     

Polymorphism of rs873308 near the transmembrane protein 57 gene is associated with serum lipid levels

SNP (single-nucleotide polymorphism) of rs10903129 near the TMEM (transmembrane protein) 57 locus has been associated with TC (total cholesterol) in a previous GWAS (genome-wide association study), but the association of TMEM57 rs873308 SNP and serum lipid levels has not been previously reported. The current study was undertaken to detect the association of the TMEM57 rs873308 SNP and several environmental factors with serum lipid profiles in the Han Chinese and Mulao populations. The genotypes of the TMEM57 rs873308 SNP in 865 individuals of Han Chinese and 902 participants of Mulao nationality were determined by PCR and RFLP (restriction-fragment-length polymorphism) combined with gel electrophoresis and then confirmed by direct sequencing. The T allele frequency of TMEM57 rs873308 SNP was not different between Han and Mulao (23.18% versus 25.72%, P>0.05), but different between males and females in the two ethnic groups (P<0.05). The T allele carriers had lower serum TC, Apo (apolipoprotein) B, HDL-C (high-density lipoprotein cholesterol) levels, ApoA1/ApoB ratio in Han; and lower TAG (triacylglycerol), LDL-C (low-density lipoprotein cholesterol), ApoA1 levels and the ApoA1/ApoB ratio and higher HDL-C levels in Mulao than the T allele non-carriers. There was also different association of the TMEM57 rs873308 SNP and serum lipid profiles between males and females in the both ethnic groups. Serum lipid parameters in the two ethnic groups were also associated with several environmental factors. The association of the TMEM57 rs873308 SNP and serum lipid levels was different in the Han Chinese and Mulao populations and between males and females in the both ethnic groups. There may be a sex-specific association of the TMEM57 rs873308 SNP and serum lipid levels in our study populations.     

Allelic Combinations of Immune Response Genes and Risk of Development of Myocardial Infarction

Myocardial infarction (MI) is a multifactorial polygenic disease. It develops because of the complex interaction between many environmental and genetic factors. In this paper, we have studied associations of MI and allele combinations of 17 polymorphic markers of immune response genes in an ethnically homogeneous group of Tatars. The material for analysis was DNA samples of patients (286 men) with onset of MI at the age of 30 to 60 years and 301 essentially healthy men of the control group. Using the APSampler algorithm, we obtained allele combinations with the increased risk of MI in which allele variants CX3CR1*M (rs3732378), VCAM1*C (rs3917010), ICAM1*E (rs5498), LTA*A (rs909253), and TNFRSF1B*M (rs1061622) occurred the most often.     

Polymorphisms of the gene encoding cholesterol ester transfer protein and serum lipoprotein levels in subjects with and without coronary heart disease

Summary We determined TaqI-A, TaqI-B and EcoNI genotypes at the cholesteryl ester transfer protein (CETP) locus in 111 healthy volunteers and in 187 hyperlipidemic men of whom 72 had suffered a myocardial infarction. There were no significant differences in the allele distributions at these polymorphic loci either between the population sample and the hyperlipidemic subjects, or between patients with and without previous myocardial infarction. To detect the associations between the CETP polymorphisms and serum lipid and apoprotein levels, we determined the serum concentrations of total cholesterol, triglycerides, high density lipoprotein (HDL)-cholesterol, apoA-I, apoA-II and apoB in the subjects studied and correlated them to the 3 RFLPs. No significant differences were observed in the serum levels of apoproteins and lipid parameters between subjects with different genotypes in any of these polymorphic CETP loci, either in the population sample or in hyperlipidemic men. Multivariate analyses did not reveal a significant independent role for any of the 3 polymorphisms in determining serum HDL-cholesterol or apoA-I levels after adjusting for triglyceride and low density lipoprotein cholesterol concentrations. This was evident for the group of healthy volunteers and for hyperlipidemic subjects, including those who had survived a myocardial infarction. We conclude that, in Finns, the CETP RFLPs are not useful markers for the risk of coronary heart disease.     

Association of deoxyribonuclease I genetic polymorphisms with myocardial infarction in Han Chinese

Deoxyribonuclease I gene exhibits polymorphisms, including a single nucleotide polymorphism (A2317G) and a 56 bp variable number of tandem repeat, designated as HumDN1. G2317 was regarded as an independent risk factor for Japanese myocardial infarction (MI) patients. We investigated the association between either A2317G or HumDN1 polymorphism of deoxyribonuclease I gene and MI in Han Chinese population. A2317G and HumDN1 polymorphisms in 278 MI patients and 297 unrelated controls were detected by PCR and PCR-restriction fragment length polymorphism. Plasma lipids were measured in fasting state by biochemical methods. A new HumDN1 genotype -HumDN1 4/6 was found in Han Chinese MI patients. Genotype distributions and allele frequencies of A2317G and HumDN1 did not differ between MI patients and control group (all P > 0.05). In addition, none of estimated haplotypes significantly increased or decreased the risk of MI. In analysis of covariance, plasma total cholesterol was observed to be associated with HumDN1 genotypes in MI patients (P = 0.02). Our data suggest HumDN1 genotypes are related to total cholesterol levels in Han Chinese MI patients, but deoxyribonuclease I gene polymorphisms are not associated with susceptibility to MI in Han Chinese.     

Association of Glutathione S-Transferase theta 1 and mu 1 Genes Polymorphisms with the Susceptibility of Myocardial Infarction in Bangladesh

Background:Myocardial infarction is one of the leading causes of morbidity and mortality worldwide. Oxidative stress plays a vital role in the pathogenesis of atherosclerosis leading to myocardial infarction and Glutathione S-transferases (GSTs) act as detoxifying enzymes to reduce oxidative stress. The aim of the present study was to investigate the associations of the GST (T1 & M1) gene polymorphism with the susceptibility of myocardial infarction in the Bangladeshi population.Methods:A case-control study on 100 cardiac patients with MI and 150 control subjects was conducted. The genotyping of GST (T1 & M1) gene was done using conventional Polymerase Chain Reaction.Results:The percentage of GSTM1 genotypes was significantly (p< 0.01) lower in patients compared to control subjects while the GSTT1 genotypes were not significantly different between the study subjects. The individual with GSTM1 null allele was at 2.5-fold increased risk {odds ratio (OR)= 2.5; 95 % confidence interval (95 % CI)= 1.4 to 4.3; p< 0.01} of experiencing MI while individual with either GSTM1 or GSTT1 genotypes was at lower risk. In the case of GST M1 and GST T1 combined genotype, patients having both null genotypes for GST M1 and GST T1 gene showed significantly (p< 0.01) higher risk of experiencing MI when compared to control subjects (OR= 3.5; 95% CI= 1.7–7.2; p< 0.001). Conclusion:Thus our recent study suggested that GSTM1 alone and GSTM1 and T1 in combination augments the risk of MI in Bangladeshi population. Key Words: Bangladesh, GST (T1 & M1), Myocardial infarction, PCR, Polymorphism     

Tetra primer ARMS-PCR relates folate/homocysteine pathway genes and ACE gene polymorphism with coronary artery disease

Cardiovascular disorders and coronary artery disease (CAD) are significant contributors to morbidity and mortality in heart patients. As genes of the folate/homocysteine pathway have been linked with the vascular disease, we investigated association of these gene polymorphisms with CAD/myocardial infarction (MI) using the novel approach of tetraprimer ARMS-PCR. A total of 230 participants (129 MI cases, 101 normal subjects) were recruited. We genotyped rs1801133 and rs1801131 SNPs in 5'10' methylenetetrahydrofolate reductase (MTHFR), rs1805087 SNP in 5' methyltetrahydrofolate homocysteine methyltransferase (MTR), rs662 SNP in paroxanse1 (PON1), and rs5742905 polymorphism in cystathionine beta synthase (CBS). Angiotensin converting enzyme (ACE) insertion/deletion polymorphism was detected through conventional PCR. Covariates included blood pressure, fasting blood sugar, serum cholesterol, and creatinine concentrations. Our results showed allele frequencies at rs1801133, rs1801131, rs1805087 and the ACE insertion/deletion (I/D) polymorphism varied between cases and controls. Logistic regression, after adjusting for covariates, demonstrated significant associations of rs1801133 and rs1805087 with CAD in the additive, dominant, and genotype model. In contrast, ACE I/D polymorphism was significantly related with CAD where recessive model was applied. Gene-gene interaction against the disease status revealed two polymorphism groups: rs1801133, rs662, and rs1805087; and rs1801131, rs662, and ACE I/D. Only the latter interaction maintained significance after adjusted for covariates. Our study concludes that folate pathway variants exert contributory influence on susceptibility to CAD. We further suggest that tetraprimer ARMS-PCR successfully resolves the genotypes in selected samples and might prove to be a superior technique compared to the conventional approach.     

Genetic Variations in the Vitamin D Receptor Predict Type 2 Diabetes and Myocardial Infarction in a Community-Based Population: The Troms? Study

BackgroundThough the associations between low serum 25-hydroxyvitamin D (25(OH)D) levels and health outcomes such as type 2 diabetes (T2D), myocardial infarction (MI), cancer, and mortality are well-studied, the effect of supplementation with vitamin D is uncertain. This may be related to genetic differences. Thus, rs7968585, a single nucleotide polymorphism (SNP) of the vitamin D receptor (VDR), has recently been reported as a predictor of composite health outcome. We therefore aimed to evaluate whether rs7968585 predicts separate clinical outcomes such as T2D, MI, cancer, and mortality in a community-based Norwegian population.ConclusionsThe VDR-related SNP rs7968585 minor allele is a significant and positive predictor for T2D and possibly for MI. Since the functional mechanism of this SNP is not yet understood, and the association with T2D is reported for the first time, confirmatory studies are needed.     

Genetic association of lipid metabolism related SNPs with myocardial infarction in the Pakistani population

Myocardial infarction (MI) is the major cardiovascular disease. This can be caused by mutual interaction of environmental and genetic factors. The current study was designed to investigate the role of lipid metabolism related genetic polymorphisms with the onset of MI in Punjabi population of Pakistan. A total of 384 subjects was studied from April 2011 to July 2012. To determine the genetic associations with MI, the single nucleotide polymorphisms (SNPs) were genotyped by sequencing, as well as one label extension method. Out of eight SNPs in four candidate genes, seven genetic variants were significantly (P < 0.05) associated with elevated risk of MI. In current study two SNPs rs662799 risk allele G (P = 0.03) and rs3135506 risk allele C (P = 0.05) of APOA5 were found to be associated with significant higher risk of triglyceride levels, irrespective of age, sex, obesity, diabetes, hypertension and smoking. Gene variants (rs1558861, rs662799 and rs10750097) in APOA5 showed almost complete linkage disequilibrium and their minor allele frequencies (0.34, 0.28, and 0.41 respectively) were more prevalent (P < 0.05) in cases than controls. We further revealed risk haplotypes (C-T-G-A, G-C-A-G; P = 0.001) and protective haplotypes (G-T-A-G, C-C-G-A; P = 0.005) between these four SNPs for the progression of MI. Current study confirms the correlation between lipid metabolism related SNPs with MI and supports the role of APOA5 in raising plasma triglyceride levels in Pakistanis. However further studies are needed for delineating the role of these SNPs.     

TOMM40 gene polymorphisms association with lipid profile

The distribution of the allele and genotype frequency for the TOMM40 gene polymorphic variants rs741780, rs157580, rs1160985, rs2075650, and rs8106922 was analyzed in a sampling of ethnic Russians from the city of Kemerovo. The study of the structure of linkage disequilibrium in terms of five studied polymorphic variants showed the presence of a haplotype block 2 Kb in length, which includes three polymorphic variants, i.e., rs741780, rs1160985, and rs8106922. The differences in the frequencies of alleles and genotypes in terms of the polymorphic rs2075650 and rs157580 variants between ethnic Russians from the city of Kemerovo and other European populations were detected. It was discovered that polymorphic variants of TOMM40 rs741780, rs1160985, and rs8106922 are associated with serum triglyceride concentrations. In men, the polymorphic variant rs2075650 is associated with low-density lipoprotein cholesterol levels. In women, the polymorphic variant rs741780 is associated with diastolic blood pressure levels.     

FADS2 rs3834458基因多态性与中国汉族人群冠心病易感性的相关性研究

目的:探讨脂肪酸去饱和酶2(FADS2)基因rs3834458位点多态性与中国汉族人群冠心病易感性的关系。方法:随机抽取青岛地区汉族人群中149名无血缘关系的健康体检人群为对照组以及我院收治的192例冠心病患者为冠心病组。采用聚合酶链反应(PCR)对健康人群、冠心病患者进行FADS2 rs3834458基因分型,检测受试者的生化指标,采用x2检验、t检验、Wilcoxon秩和检验和Logistic回归进行统计学分析。结果:冠心病组男性比例、年龄、体重指数(BMI)、血糖(GLU)、总胆固醇(TC)、甘油三脂(TG)、低密度脂蛋白(LDL-C)、丙氨酸氨基转移酶(ALT),天冬氨酸氨基转移酶(AST)、γ-谷氨酰转移酶(GGT)、碱性磷酸酶(ALP)均显著高于对照组(P0.05),而高密度脂蛋白(HDL-C)水平明显低于对照组(P0.05)。两组间的基因型分布和等位基因频率比较无显著差异(P0.05)。性别(男性)、年龄、GLU、TC和HDL-C(1.00 mmol/L)是冠心病发生的独立危险因素(OR=3.57,1.14,1.34,3.50,2.89)。FADS2rs3834458有T/T、T/del、del/del三种基因型,而T等位基因不是冠心病发生的独立危险因素(P=0.641)。结论:FADS2 rs3834458基因多态性与中国汉族人群中冠心病发病风险无明显相关性。     

乙型肝炎病毒不同基因分型与淋巴细胞亚群分布、肝功能及脂代谢的关系

目的:探讨乙型肝炎病毒(HBV)不同基因分型与淋巴细胞亚群分布、肝功能及脂代谢的关系。方法:选择2016年10月-2017年12月在我院治疗的HBV患者130例,将患者进行HBV基因分型检查,根据不同基因分型将患者分为B型组(n=59)和C型组(n=71),采用实时荧光PCR法检测血清HBV-DNA载量,采用ADVIA2400全自动生化分析仪测定患者丙氨酸转氨酶(ALT)、白蛋白(ALB)、总胆红素(Tbil)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平,采用美国ACL-TOP700血凝仪检测凝血酶原时间(PT)。采用流式细胞仪测定不同基因分型患者CD3~+、CD4~+、CD8~+及CD4~+/CD8~+水平。结果:两组患者HBV-DNA载量、PT比较差异无统计学意义(P0.05);B型组患者ALT、ALB、TbiL水平均低于C型组(P0.05)。B型组患者CD3~+、CD4~+、CD4~+/CD8~+水平均高于C型组,CD8~+水平低于C型组(P0.05)。两组患者TC、TG、HDL-C和LDL-C水平比较差异无统计学意义(P0.05)。结论:不同基因分型对HBV患者病毒复制能力及脂代谢无明显影响,但C型HBV对患者免疫功能及肝功能损伤更严重。     

A TagSNP in SIRT1 Gene Confers Susceptibility to Myocardial Infarction in a Chinese Han Population

SIRT1 exerts protective effects against endothelial cells dysfunction, inflammation and atherosclerosis, indicating an important role on myocardial infarction (MI) pathogenesis. Nonetheless, the effects of SIRT1 variants on MI risk remain poorly understood. Here we aimed to investigate the influence of SIRT1 polymorphisms on individual susceptibility to MI. Genotyping of three tagSNPs (rs7069102, rs3818292 and rs4746720) in SIRT1 gene was performed in a Chinese Han population, consisting of 287 MI cases and 654 control subjects. In a logistic regression analysis, we found that G allele of rs7069102 had increased MI risk with odds ratio (OR) of 1.57 [95% confidence interval (CI) = 1.15–2.16, Bonferroni corrected P (P_c) = 0.015] after adjustment for conventional risk factors compared to C allele. Similarly, the combined CG/GG genotypes was associated with the increased MI risk (OR = 1.64, 95% CI = 1.14–2.35, P_c = 0.021) compared to the CC genotype. Further stratified analysis revealed a more significant association with MI risk among younger subjects (≤ 55 years old). Consistent with these results, the haplotype rs7069102G-rs3818292A-rs4746720T containing the rs7069102 G allele was also associated with the increased MI risk (OR = 1.41, 95% CI = 1.09–1.84, P_c = 0.040). However, we did not detect any association of rs3818292 and rs4746720 with MI risk. Our study provides the first evidence that the tagSNP rs7069102 and haplotype rs7069102G-rs3818292A-rs4746720T in SIRT1 gene confer susceptibility to MI in the Chinese Han population.     

12周高强度间歇训练对不同基因型载脂蛋白E血脂异常人群的调脂作用

目的:观察12周高强度间歇训练(HIIT)对不同载脂蛋白E(ApoE)基因型血脂异常人群的血脂调节作用。方法:通过测试空腹血脂指标,筛选出88例血脂异常患者作为受试对象,采集受试对象口腔粘膜进行载脂蛋白E基因型检测,测定12周高强度间歇训练干预前后的血脂水平。结果:88例血脂异常者中共检测出5种基因型,其分布为ApoE3/3＞ApoE3/4 ＞ApoE2/3＞ApoE2/2＞ApoE2/4,等位基因ε3＞ε2=ε4。运动干预前,血脂异常人群中ε4等位基因组的总胆固醇水平显著高于ε2和ε3基因组(P＜0.01),低密度脂蛋白胆固醇水平显著高于ε2基因组(P＜0.05),其余指标在各组间无显著性差异(P＞0.05)。12周的高强度间歇训练显著降低ε3基因组血清总胆固醇、甘油三酯和低密度脂蛋白胆固醇水平,升高高密度脂蛋白胆固醇水平。ε4基因组在运动干预后血清总胆固醇和低密度脂蛋白胆固醇降低,甘油三酯和高密度脂蛋白胆固醇无显著性改变。ε2基因组在运动干预后血清脂质无明显改善。结论:血脂异常人群载脂蛋白E基因多态性影响运动的调脂效果,12周高强度间歇训练可以作为ε3和ε4等位基因携带者调节血脂的运动干预方式。     

Apolipoprotein A5 polymorphisms in Turkish population: association with serum lipid profile and risk of ischemic stroke

Atherosclerosis, a major cause of ischemic stroke, may be associated with variability of triglyceride (TG) levels. Apolipoprotein A5 (APOA5) genetic polymorphisms are associated with altered TG levels. The objective of this study was to investigate the coding region polymorphisms S19W (rs3135506) and G185C (rs2075291) and the promoter region polymorphism ?1131T>C (rs662799) of the APOA5 gene as risk factors for ischemic stroke in Turkish population. Study group consisted of 272 ischemic stroke patients and 123 controls. Genotypes were determined by real-time polymerase chain reaction (PCR) for S19W and PCR-restriction fragment length polymorphism analysis (PCR–RFLP) for ?1131T>C and G185C. 19W allele frequency was 0.090 in stroke patients and 0.062 in controls (P = 0.191). Minor allele frequencies of ?1131T>C and G185C in patients were 0.106 and 0.004, respectively, and were nearly the same in controls. Total cholesterol and LDL-cholesterol levels were significantly higher for stroke patients having at least one 19W allele compared to non-carriers. A significant difference was also found for LDL-cholesterol levels of stroke patients; higher in ?1131C allele carriers compared to wild type patients. There was a trend for higher frequency of ischemic stroke among ?1131C allele carrier hypertensive, diabetic or obese subjects compared to non-carriers. However, APOA5 genotypes were not associated with the risk of ischemic stroke by logistic regression analysis. The present study demonstrated that carrying rare alleles of APOA5 S19W, ?1131T>C and G185C alone do not constitute a risk for ischemic stroke in the studied Turkish subjects.