肝脂酶基因启动子-250G/A多态性与2型糖尿病合并冠心病易感性的相关研究

目的 探讨汉族人群肝脂酶(hepatic lipase,HL)基因启动子-250G/A多态性与2型糖尿病(type 2 diabetes mellitus,T2DM)合并冠心病(coronary heart disease,CHD)的相关性.方法 采用聚合酶链反应-限制性片段长度多态性方法(polymerase chain reaction-restricted fragment length polymorphism,PCR-RFLP)检测364例T2DM+CHD组、357例T2DM组患者和356名健康对照者HL基因启动子-250G/A多态性,并分析其对脂类的影响.结果 T2DM组与对照组HL基因启动子-250G/A多态性基因型和等位基因频率差异无统计学意义(P>0.05);T2DM+CHD组GA+AA基因型频率低于对照组(0.431 vs 0.618,P=0.031);等位基因频率差异无统计学意义(P>0.05).调整混杂因素后,Spearman相关及线性回归分析,糖尿病患者(T2DM组和T2DM+CHD组),A等位基因与高密度脂蛋白胆固醇、载脂蛋白A1呈正相关;Logistic回归分析显示,A等位基因是冠心病发生的一个危险因素.结论 HL基因启动子-250G/A多态性与2型糖尿病合并冠心病的发生有关,并影响脂类代谢.     

Association of an intronic haplotype of the LIPC gene with hyperalphalipoproteinemia in two independent populations

Hepatic lipase (HL) plays a major role in the regulation of plasma lipids. Several groups seeking to find association between the gene encoding HL (LIPC) and plasma concentrations of high-density lipoprotein cholesterol (HDLc) using various methods and populations have reported conflicting results. We have approached the problem of demonstrating a relationship between the LIPC locus and HDLc by means of haplotype association using four single nucleotide polymorphisms (SNPs) (rs12594375G/A, rs8023503C/T, rs4775047C/T, and rs11634134T/A) located in intron 1 of the LIPC gene in two independent Japanese populations consisting of 2,970 and 1,638 individuals, respectively. Significant association between hyperalphalipoproteinemia and a specific haplotype in this intron was detected in both populations. When HDLc levels among the three haplotypic categories were analyzed [haplotype rs8023503C/rs12594375G (haplotype-1; H1) homozygotes (H1H1), haplotype rs8023503T/rs12594375A (haplotype-2; H2) homozygotes (H2H2), and heterozygotes (H1H2)], HDLc levels were lowest among H1H1 [mean ± standard error (SE) = 58.4 ± 0.4 mg/dl], highest among H2H2 (62.5 ± 0.8 mg/dl), and intermediate among H1H2 (59.2 ± 0.4 mg/dl) (P = 0.00011), indicating that H2 haplotype elevates plasma HDLc levels. This association was validated in the second population (n = 1,638) (P = 0.00070). The results provide convincing evidence that the LIPC locus influences HDL metabolism.     

Analysis of TGF-beta(1) gene polymorphisms in Hong Kong Chinese patients with asthma

BACKGROUND: The C-509T polymorphism of TGF-beta(1) gene has been associated with asthma and atopy in white populations. OBJECTIVE: We investigated the association between asthma and previously identified polymorphisms at C-509T and T869C of the TGF-beta(1) gene among 250 Chinese patients with asthma and 308 healthy controls in Hong Kong. METHODS: Genotyping was performed on peripheral blood genomic DNA by using PCR-RFLP. RESULTS: There were no differences in the frequencies of genotypes and alleles between patients and controls. The C-509T and T869C polymorphisms were in tight linkage disequilibrium (P < .01). Among atopic subjects, significant differences were found in genotype and allele frequencies for T869C polymorphism between patients and controls (P = .014 and P = .019, respectively), and individuals bearing the CC genotype were associated with increased risk for the development of asthma (odds ratio, 2.58; 95% CI, 1.17-5.66; P = .018) after adjusting for age, sex, and smoking status. Individuals with asthma bearing the CT genotype of the C-509T polymorphism had significantly increased risk for severe airflow obstruction compared with individuals who had mild obstruction (odds ratio, 4.00; 95% CI, 1.06-15.08; P = .035). CONCLUSION: Our results indicate that the polymorphisms at C-509T and T869C of the TGF-beta(1) gene are associated with asthma susceptibility in atopic subjects of the Hong Kong Chinese population, and the C-509T polymorphism may play a role in the pathogenesis of airflow obstruction.     

TLR4/Asp299Gly, CD14/C-260T, plasma levels of the soluble receptor CD14 and the risk of coronary heart disease: The PRIME Study

TLR4 and CD14 are two components of the LPS receptor complex, which are considered to play a key role in the pathogenesis of atherosclerosis. TLR4/Asp299Gly and CD14/C-260T polymorphisms are thought to modulate the activity of this complex. The aim of the study was to examine the association between the TLR4/Asp299Gly and CD14/C-260T polymorphisms, plasma levels of the soluble receptor CD14 (sCD14), and the incidence of coronary heart disease (CHD) in a prospective cohort (the PRIME Study) of 9758 healthy men aged 50-59 years recruited in France and Northern Ireland. A nested case-control design was used, comparing the 249 participants who developed a CHD event during the 5-year follow-up with 492 population- and age-matched control subjects. The two polymorphisms were genotyped and baseline plasma concentrations of sCD14 were measured. None of the two polymorphisms, or sCD14 levels, either considered alone or in combination, were associated with the risk of CHD. The CD14/C-260T allele was associated with increased plasma concentrations of soluble thrombomodulin and vascular cell adhesion molecule-1 and, to a lesser extent, sCD14. No relationship was observed between the TLR4 polymorphism and, any of the inflammatory and endothelial markers measured. The TLR4/Asp299Gly and CD14/C-260T polymorphisms and plasma sCD14 concentrations do not appear as significant predictors of the risk of CHD in healthy individuals.     

Effects of hepatic lipase gene promoter nucleotide variations on serum HDL cholesterol concentration in the general Japanese population

Genetic factors may play a major role in determining serum high-density lipoprotein (HDL) cholesterol (HDL-C) levels in the general population. Cholesteryl ester transfer protein (CETP) is a strong genetic factor as a determinant of HDL-C levels in Japanese, whereas hepatic lipase (HL) plays a predominant role in Caucasian populations. We investigated the effects of HL gene promoter polymorphisms on HDL-C levels in a general population of Japanese men (n = 299). An HL promoter polymorphism of −514C/T explained a considerable variance of HDL-C (2.9%), as compared with CETP mutations of D442G and IVS14 + 1G > A (3.6% and 1.9%). HL promoter variation of the −514C/C genotype, reported to have high HL activity, had significant effects on decreasing HDL-C levels (−3.8 mg/dl), but −514T allele carriers had a weak effect on increasing HDL-C levels. The frequency of the −514T allele was three times higher (0.50) in the Japanese than in Caucasian populations (0.15–0.19). Thus, the higher frequency of the HL−514T allele, along with CETP gene mutations, could explain about 9% of phenotypic variability of HDL-C. These genetic attributes may be among the many factors that contribute to the relatively higher serum HDL-C levels in Japanese subjects. Received: November 9, 2000 / Accepted: January 5, 2001     

A common truncation variant of lipoprotein lipase (Ser447X) confers protection against coronary heart disease: the Framingham Offspring Study

Genetic variation at the lipoprotein lipase (LPL) locus has been shown to influence plasma lipids and to modulate risk of coronary heart disease (CHD). Recently, we found that the most frequent variant at this locus, involving a C-terminal truncation of two amino acids (Ser447X), was associated with both higher LPL activity and high density lipoprotein cholesterol (HDL-C) in patients with CHD. However, the impact of this S447X variant on lipids and CHD in the general population was hitherto unknown. We, therefore, analyzed a total of 1114 men and 1144 women randomly ascertained from the Framingham Offspring Study (FOS) for the presence of this LPL variant. Carrier frequency of the S447X allele was 17%, and in men carrier status was associated with higher total cholesterol (delta = 6.2 mg/dl, p = 0.03). higher HDL-C (delta = 2.3 mg/dl, p = 0.01), and lower triglyceride (TG) levels (delta = -19.4 mg/dl, p = 0.02). Moreover, in men, the S447X allele conferred significant protection against CHD (odds ratio: 0.43; p = 0.04). These effects on lipids and CHD were not seen in women. Our study represents the first report on the impact of this mutation on CHD in men from the general population, and we conclude, therefore, that the S447X variant may confer significant protection against high TG levels, low HDL-C, and premature CHD in these subjects.     

Association between VEGF polymorphisms (936c/t, -460t/c and -634g/c) with haplotypes and coronary heart disease susceptibility

Aim: Our aim was to investigate the association between single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor (VEGF) and coronary heart disease (CHD) susceptibility in Chinese Han population. Methods: 144 CHD patients and 150 healthy individuals were enrolled in the study. Three SNPs (936C/T, -460T/C and -634G/C) of VEGF were chose and then were genotyped with Sequenom time-of-flight mass spectrometry (TOFMS). Odds ratio (OR) with 95% confidence interval (CI) were used to evaluate the association of genotypes and haplotypes and CHD susceptibility. Results: The frequencies of -460T/C CC genotype (13.6%) was found higher in the case group than that of control group (6.7%), which indicated that CC genotype was a risk factor for CHD (OR=2.50, 95% CI=1.10-5.68). Correspondently, the C allele appeared to increase the risk of CHD (OR=1.54, 95% CI=1.07-2.22). For -634G/C polymorphism, the risk of the CC genotype carrier for CHD increased 2.24 fold compared to the wild genotype. Moreover, -634G/CC allele was significantly associated with CHD susceptibility (OR=1.65, 95% CI=1.15-2.36). In addition, +936C/T CT genotype and C allele appeared to be a genetic-susceptibility factors for CHD (OR=2.43, 95% CI=1.44-4.10; OR=1.95, 95% CI=1.26-3.02). The haplotype analysis showed that T-C-T, C-C-C and C-G-C haplotypes all could increase the risk for CHD (OR: 2.43, 2.77 and 2.33). Conclusion: we concluded VEGF polymorphisms were associated with CHD susceptibility. Moreover, the haplotypes of T-C-T, C-C-C and C-G-C all could increase the risk for CHD.     

Genetic variants of the IL13 and IL4 genes and atopic diseases in at-risk children

We studied a cohort containing 368 children at high risk of developing atopy and atopic disorders and 540 parents of those children to investigate whether the IL13 Arg130Gln and C-1112 T polymorphisms were associated with these outcomes. We also investigated whether haplotypes consisting of any two polymorphisms of IL13 Arg130Gln, IL13 C-1112 T and IL4 C-589 T were associated with these phenotypes. In 288 white children, the IL13 130Gln allele was associated with atopy (RR=1.9, P=0.047), and with atopic dermatitis (RR=2.5, P=0.014). The associations were confirmed using a family-based test of association (P=0.027 and 0.030, respectively) in all subjects. In white subjects there were associations of haplotypes consisting of IL13 Arg130Gln and IL4 C-589 T with atopic dermatitis (P=0.006) and with atopy (P=0.009). Our data suggest that the IL13 Arg130Gln polymorphism and haplotypes consisting of IL13 Arg130Gln and IL4 C-589 T were associated with the development of atopy and atopic dermatitis at 24 months of age.     

CD14启动子-159位点基因多态性与冠状动脉粥样硬化性心脏病的相关性研究

目的研究湖北地区汉族人群CD14启动予-159（C→T）多态性分布，探讨该多态性与冠状动脉粥样硬化性心脏病（冠心病）的相关性。方法应用聚合酶链反应-限制性片段长度多态性技术对湖北地区汉族162例冠心病患者及196名正常对照组者CD14基因启动子-159位点进行基因型分析。结果CD14启动子-159位点基因型频率和等位基因频率在冠心病组和对照组间比较差异有统计学意义，（基因型：X^2=0．654，P〈0．05，CT vs CC，OR=1．245，95％CI：1．001～1．473，TT vs CC，OR=2．374，95％CI：2．012～2．649；等位基因：X^2=0．547，P〈0．05，TvsC，X^2=0、547，P〈0、05，OR=3．105，95 ％CI：2．493～3．539）：CD14启动子-159位点基因型频率和等位基因频率在非心肌梗塞组和心肌梗塞组间比较差异有统计学意义（基因型：X^2=0．782，P〈0．05，CF vs CC，OR=2．375，95％CI：2．017～2．689，TT vs CC．OR=3．459，95％CI：3．003～3．846；等位基因：X^2=2．374，P〈0．05，T vs C，X^2=2．374，P〈0．05，OR=4．011，95％CI：3．814～4．279），然而，我们没有发现往冠心病狭窄血管支数之间存存差异。结论CD14启动子-159（C→T）基因多态性中的T等位基因可能是心肌梗塞的遗传学风险因素。     

血管内皮生长因子基因多态性与先天性心脏病相关性的Meta分析

目的 评价血管内皮生长因子（VEGF）等位基因、基因型、基因单倍型多态性与先天性心脏病（CHD）的相关性.方法 检索Cochrane图书馆、Medline、PubMed、EMBASE、中国期刊全文数据库、万方数据库及中国生物医学文献数据库,检索起止时间均为建库至2011年12月,并且对重要文献的参考文献采取手工回溯检索.获取VEGF与CHD相关性的病例对照研究和传递不平衡检验文献.对文献进行质量评价.采用RevMan 5.1.1软件进行异质性检验,根据检验结果选择适当的效应模型进行Meta分析.结果 6篇文献共10项独立研究纳入分析,漏斗图检验存在发表偏倚.Meta分析结果显示：① VEGF C-2578A和G-1154A位点等位基因变异显著增加DiGeorge综合征患者的CHD易感性,OR分别为1.40（95%CI：1.04～1.16）和1.87（95%CI：1.27～2.75）;G-634C位点的等位基因变异显著增加普通病例的CHD易感性,OR=1.29,95%CI：1.02～1.62.② G-1154A位点（AA＋AG）为DiGeorge综合征患者合并CHD的危险因素,OR=2.10,95%CI：1.32～3.34.③单倍型AAG在DiGeorge综合征患者中显著增加CHD易感性,OR=1.82,95%CI：1.31～2.54;单倍型CGC显著降低普通病例CHD风险的保护作用,OR=0.79,95%CI：0.63～0.99.结论 VEGF等位基因、基因型、基因单倍型多态性与CHD易感性存在一定的相关性,且在DiGeorge综合征患者与普通患者间存在差异;在不伴DiGeorge综合征的人群中,特定单倍型（CGC）则有显著降低CHD风险的保护作用,其作用机制尚需进一步明确.     

Cathepsin S genotypes are associated with Apo-A1 and HDL-cholesterol in lean and obese French populations

Cathepsin S (CTSS) is a cysteine protease that has a central role in remodeling the extracellular matrix and, as such, has been implicated in the etiology of cardiovascular disease. This study used five tag single nucleotide polymorphisms (tSNPs) to screen the CTSS gene in healthy lean ( n  = 1891) and obese French populations ( n  = 477) for their association with various phenotypes: body mass index, waist-to-hip ratio, glycemia, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (Apo-A1) and apolipoprotein B. Significant associations were identified between rs11576175 tSNP (A/G) and Apo-A1 and HDL-C plasma levels in a sex-specific manner. Lean female subjects homozygous for the minor A-allele had higher levels of circulating Apo-A1 (p = 0.0003), while lean male A/A carriers had higher levels of HDL-C (p = 0.007) compared with the other genotypes. In the obese cohort, associations were found between three tSNPs and Apo-A1 levels in adult female subjects: rs10888390 (G/A), p = 0.01; rs10888394 (T/C), p = 0.03; and rs1136774 (C/T), p = 0.02; however, only rs10888390 remained significant in a combined model (p = 0.03). These results provide the first evidence that CTSS sequence variations are associated with two human metabolic risk factors for cardiovascular diseases: plasma Apo-A1 and HDL-C concentrations.     

Association of ATP-binding cassette transporter A1 gene polymorphisms with plasma lipid variability and coronary heart disease risk

Objective: Our study aimed to investigate the association of ABCA1 polymorphisms with plasma lipid variability and CHD risk in the Chinese Han population. Methods: 754 CHD patients and 760 controls were included in this case-control study. Three SNPs (rs363717, rs4149339, and rs4149338) in ABCA1 3’UTR and one nonsynonymous SNP (rs2230808) in ABCA1 exon 35 were selected and genotyped. The analysis of genetic data was performed using the SNPstats program and the SPSS17.0 software. Results: Significant associations were observed between SNP rs363717 and CHD risk under different genetic models before or after Bonferroni corrections (codominant model: OR = 0.70, P = 0.003 for AG vs. AA; dominant model: OR = 0.71, P = 0.003 for GG + AG vs. AA). The nonsynonymous SNP rs2230808 was associated with higher total cholesterol levels (P = 0.047). The GCC haplotype (consisting of alleles of SNPs rs363717, rs4149339, and rs4149338) was associated with a decreased risk of CHD (OR = 0.8, P = 0.027). Three ABCA1 SNPs interacted with high triglyceride levels to increase CHD risk (P values of interactions were 0.010 for rs363717, 0.010 for rs4149339, and 0.020 for rs4149338, respectively). Conclusions: Our results suggest that ABCA1 polymorphisms influence plasma lipid variability and CHD risk. ABCA1 polymorphisms could also modify the effects of plasma lipids on CHD risk.     

Polymorphisms of transforming growth factor-β1 associated with increased risk of gastric cardia adenocarcinoma in north China

Transforming growth factor beta 1 (TGF-β1) is a multifunctional cytokine that has been implicated in the oncogenesis and tumour progression. However, the association of TGF-β1 polymorphism with gastric cardia adenocarcinoma (GCA) remains unclear. The aim of the study was to investigate the possible association of the polymorphisms of TGF-β1 with susceptibility to GCA in a population of north China. A case-control analysis was performed to assess the association of six single nucleotide polymorphisms (SNPs) of TGF-β1 and GCA risk. The genotype and allele distributions of TGF-β1 G-800A, C-988A, G915C and C788T in GCA patients were not significantly different from that in healthy controls (P>0.05). The -509T and 869C allele significantly elevated the risk of developing GCA (adjusted OR=1.45 and 1.41; 95% CI=1.04-2.10 and 1.07-2.08, respectively). The CT and TT genotype of C-509T and the TC and CC genotype of T869C significantly elevated the risk of developing GCA. When stratified by tumour stage, the -509T and 869C allele carriers had an increased risk of TNM stage III+IV GCA as compared with noncarriers. The C-509T and T869C SNP are in a strong linkage disequilibrium (D'=0.94). Compared with C/T haplotype, T/C haplotype significantly increased the risk of developing GCA. The TGF-β1 level and expression were higher in GCA patients with -509T or 869C allele than in those without T or C allele (P<0.05). GCA patients with -509TT and 869CC genotype had higher apoptotic tumour-infiltrating lymphocytes in their cancer tissues than those with -509CC and 869TT genotype. In all, TGF-β1 C-509T and T869C polymorphisms may be associated with an increased risk of GCA in north China.     

MMP2 promoter polymorphism (C-1306T) and risk of recurrence in patients with hepatocellular carcinoma after transplantation

Genetic variants in matrix metalloproteinase (MMP) gene may influence the biological function of these enzymes and change their role in carcinogenesis and progression. The effect of MMP2 C-1306T and MMP9 C-1562T polymorphisms on genetic susceptibility has been investigated in various kinds of cancer. However, the relationship between these polymorphisms and risk of recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) has not been reported. The present study was designed to investigate the association of these two loci with the risk of HCC recurrence in 93 HCC patients treated with LT. Genotyping was performed using direct DNA sequencing. For MMP2 C-1306T variant, patients with CT heterozygous conferred a 58% reduction in recurrence risk (risk ratio: 0.419; 95% confidence interval: 0.177–0.994). The mean recurrence-free survival for CT genotype was significantly longer than that for homozygous CC patients (30.4 vs 19.3 months, p = 0.019). However, no association was found between MMP9 C-1562T polymorphisms and recurrence of HCC (p = 0.259). These findings suggest that MMP2 promoter polymorphisms may provide some predictive value for HCC recurrence after LT.     

No association of functional polymorphisms in methlylenetetrahydrofolate reductase and the risk and minor physical anomalies of schizophrenia in Korean population

Methylenetetrahydrofolate reductase (MTHFR), a critical enzyme in folate metabolism, plays an important role in DNA methylation. It has been suggested that abnormal DNA methylation contributes to the pathogenesis of schizophrenia and congenital anomalies. The previous findings regarding the genetic relationship between MTHFR and schizophrenia are controversial. This study investigated the association of the two functional polymorphisms of MTHFR, C677T and A1298C, with the risk for schizophrenia. Furthermore, we conducted an updated meta-analysis on the two polymorphisms. In addition, we investigated the relationship between the polymorphisms and minor physical anomaly (MPA), which may represent neurodevelopmental aberrations in 201 schizophrenia patients and 350 normal control subjects. There was no significant association between either of the two polymorphisms and the risk of schizophrenia (chi-square = 0.001, df = 1, P = 0.971 for C677T; chi-square = 1.319, df = 1, P = 0.251 for A1298C). However, in meta-analysis, the C677T polymorphism showed a significant association in the combined and Asian populations (OR = 1.13, P = 0.005; OR = 1.21, P = 0.011, respectively) but not in the Korean and Caucasian populations alone. Neither polymorphism was associated with MPAs measured by the Waldrop scale (chi-square = 2.513, df = 2, P = 0.285). In conclusion, the present findings suggest that in the Korean population, the MTHFR polymorphisms are unlikely to be associated with the risk for schizophrenia and neurodevelopmental abnormalities related to schizophrenia.     

Meta-Analysis of the Association of the Rs2234693 and Rs9340799 Polymorphisms of Estrogen Receptor Alpha Gene with Coronary Heart Disease Risk in Chinese Han Population

Objective: The association between a common variant of the ESR1 gene rs2234693 and rs9340799 polymorphisms with coronary heart disease (CHD) have been reported, but the available data on this relationship are inconsistent. A meta-analysis was performed to quantitative analysis the association of ESR1 gene polymorphisms and CHD risk using previous case-control studies in Chinese Han population.Methods: Several electronic databases were searched for relevant articles up to August 2012. After data collection, a meta-analysis was performed to assess heterogeneity, combine results and evaluate variations. Different effect models were used according to the difference in heterogeneity. Sensitivity analysis was assessed by omitting one study at a time. Publication bias was examined using Begg''s funnel plot and Egger''s linear regression test.Results: Ten studies covering 3400 subjects on rs2234693 and rs9340799 polymorphisms in the ESR1 gene with CHD risk was included in this meta-analysis. For rs2234693 polymorphism, ten studies were combined to the meta-analysis. A significantly increased CHD risk was found in a dominant model (OR=1.35, 955 CI=1.01-1.81, P=0.05), recessive model (OR=1.40, 95% CI=1.15-1.69, P=0.0007), and additive model (OR=1.67, 95% CI=1.19-2.34, P=0.003). Subgroup for male but not for female showed that the CC genotype could increase the risk of CHD compared with TT and TC genotype in Chinese Han population. Concerning rs9340799 polymorphism, eight studies were combined to the meta-analysis. And no evidence of significant association with CHD risk was found in all genetic models.Conclusion: Our meta-analysis of 10 studies involving Chinese Han population suggests that the CC genotype of the ESR1 rs2234693 polymorphism is significantly associated with an increased risk of CHD in males only. There was no evidence however, of a significant association between the ESR1 rs9340799 polymorphism and CHD risk.     

Genetic effect of two polymorphisms in the apolipoprotein A5 gene and apolipoprotein C3 gene on serum lipids and lipoproteins levels in a Chinese population

Two polymorphisms, apolipoprotein A5 (APOA5) -1131T>C and apolipoprotein C3 (APOC3) -482C>T, were examined in a healthy Chinese group. Analysis of covariance (ancova) showed that both -1131T>C and -482C>T minor alleles were associated with triglyceride (TG)-raising effects (p < 0.001 and p = 0.012, respectively) after adjustment of sex, age, and body mass index (BMI). Moreover, -1131T>C minor alleles were also found to be associated with total cholesterol (TC)-raising effects (p = 0.045). However, the relationship between -482C>T minor alleles and TC-raising effects was not observed after adjustment of sex, age, and BMI. By contrast, significant inverse associations were noted between minor alleles (-1131T>C and -482C>T) and high-density lipoprotein cholesterol (HDL-C) concentrations (p = 0.021 and p = 0.021, respectively). Linear regression analysis showed that the effects of -1131T>C and -482C>T polymorphisms on TG and HDL-C (0.001 and 0.008; 0.041 and 0.005, respectively) are independent and additive and that -1131T>C can seriously affect the levels of TG (0.001 vs 0.008). The additive effect of the two polymorphisms was confirmed further by haplotype analysis. Our results strongly support that the two single nucleotide polymorphisms, -1131T>C in APOA5 and -482C>T in APOC3, are related to the levels of serum TG and HDL-C and those of other several lipids and lipoproteins in the Chinese population.     

2型糖尿病患者肝脂肪酶基因标签单核苷酸多态性与血脂水平分析

观察汉族人群肝脂肪酶(HL)基因2个标签单核苷酸多态性(SNP)与2型糖尿病(T2DM)及血脂代谢的相关性.应用荧光标记单碱基延伸分型技术及寡核苷酸微阵列芯片杂交技术检测HL基因rs 12462668和rs10426971多态性.用全自动生化分析仪检测CHO、TG、HDL-C、LDL-C、载脂蛋白Al( ApoAl)及...     

Interactions and associations of paraoxonase gene cluster polymorphisms with myocardial infarction in a Pakistani population

Polymorphisms of paraoxonase gene (PON) cluster have been investigated in numerous studies for their association with myocardial infarction (MI) but the results have been conflicting. Epistasis and gene-environment interactions at this locus could possibly modulate susceptibility toward MI and account for the discrepancies. We carried out a case-control study (211 MI patients and 370 control subjects) to test association of PON cluster polymorphisms with MI, their interactions with each other and with smoking. Genotyping was performed by PCR-restriction fragment length polymorphism based assays. The Q192R, C-108T, and A148G polymorphisms were associated with MI. Two haplotypes consisting of C-108T, C311S, and A148G, having allele frequencies of 0.17 and 0.14 in the control population, predisposed to MI (global haplotype statistic chi2 = 34.74, df = 15, p = 0.0027). Multifactor dimensionality reduction analysis showed a significant three-locus model (p = 0.02) involving these three polymorphisms, suggesting a potential gene-gene interaction between PON1 and PON2. These polymorphisms also interacted with smoking, in a three-locus and a four-locus model (p = 0.01 and p = 0.05, respectively). Additionally, the R192 allele may advance the age-at-onset of MI. The PON cluster appears to be a susceptibility locus for MI in Pakistani population, and the susceptibility is modulated through gene-gene and gene-environment interactions.     

Sequence variants of the secreted phosphoprotein 1 gene are associated with total serum immunoglobulin E levels in a Japanese population

BACKGROUND: Secreted phosphoprotein 1 (SPP1) is a cytokine with pleiotrophic immunological activities, including activation of macrophage chemotaxis and T-helper type 1 (Th1) immune responses. SPP1 gene polymorphisms have been shown to be associated with several immune inflammatory diseases including multiple sclerosis (MS), which is characterized by fewer allergic symptoms and lower numbers of allergen sensitizations. OBJECTIVE: The present study examined whether SPP1 gene polymorphisms are associated with total serum IgE levels, atopy and asthma in a Japanese population. METHODS: This case-control association analysis examined 611 subjects, including 268 subjects with asthma. We genotyped three promoter and two exon polymorphisms at SPP1: -1687A/G; -381T/C; -94 deletion/G; 5891C/T; and 7052T/C. Results Association analyses of SPP1 polymorphisms showed that homozygosities for the 5891T allele (P=0.009) and 7052C allele (P=0.001) were significantly associated with increased levels of total IgE in non-asthmatic subjects. However, these variants were not associated with asthma and atopy. Interestingly, individuals carrying the 5891C allele, which is more prevalent in patients with MS in Japanese populations, displayed significantly lower levels of total serum IgE. Individuals homozygous for the 7052C allele, which is associated with development of systemic lupus erythematosus, displayed significantly higher total serum IgE levels. CONCLUSION: These findings suggest that genetic polymorphisms in SPP1 may play a role in controlling basal levels of total serum IgE, independent of atopy.