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Li-Na Zhang,
Pan-Pan Liu,
Jianqing Zhou,
R Stephanie Huang,
Fang Yuan,
Li-Juan Fei,
Yi Huang,
Limin Xu,
Ling-Mei Hao,
Xu-Jun Qiu,
Yanping Le,
Xi Yang,
Weifeng Xu,
Xiaoyan Huang,
Meng Ye,
Jiangfang Lian, Shiwei Duan
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ABSTRACT: Four gene variants related to lipid metabolism (including the rs562338 and rs503662 variants of the APOB gene, the rs7767084 variant of the LPA gene and the rs2246942 variant of the LIPA gene) have been shown to be associated with coronary heart disease (CHD). The aim of the present study was to assess their association with CHD in the Han Chinese population and to assess the contribution of these gene variants to CHD. Using the standardized coronary angiography method, we enrolled 290 CHD patients and 193 non-CHD patients as non-CHD controls from Lihuili Hospital (Ningbo, China). In addition, we recruited 330 unrelated healthy volunteers as healthy controls from the Xi Men Community (Ningbo, China). Our results demonstrated that the rs503662 and rs562338 variants of the APOB gene were extremely rare in the Han Chinese population (minor allele frequency <1%). Genotype rs2246942-GG of the LIPA gene was associated with an increased risk of CHD [CHD cases versus healthy controls: P=0.04; odds ratio (OR)=1.63; 95% confidence interval (CI)=1.02-2.60). Genotype rs7767084-CC of the LPA gene was identified as a protective factor against CHD in females (CHD cases versus non-CHD controls: P=0.04, OR=0.21; CHD cases versus healthy controls: P=0.02, OR=0.21). The results of our meta-analysis indicated that rs7767084 was not associated with a high risk of CHD (P=0.83; combined OR=0.93; 95% CI=0.47-1.85). In the present study, two single nucleotide polymorphisms (SNPs) of genes involved in lipid metabolism (rs2246942 and rs7767084) were identified to be significantly associated with CHD in the Han Chinese population. Specifically, rs2246942-GG of the LIPA gene was a risk factor for CHD, while rs7767084-CC of the LPA gene was a protective factor against CHD in females. However, our meta-analysis indicated that rs7767084 is not associated with a higher risk of CHD.
Molecular Medicine Reports 05/2013; · 0.42 Impact Factor
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ABSTRACT: The goal of our study is to evaluate the contribution of CXCL12 rs1746048 (hg19, chr10:44775574) to the risk of CHD in Han Chinese, and to summarize its role in CHD through meta-analysis of existing studies among various ethnic groups. Significant association is observed between rs1746048-C and an increased risk of CHD in Han Chinese (χ(2) = 5.41, df = 1, P = 0.02). Post hoc analysis reveals an even stronger association of rs1746048 with the risk of CHD for subjects aged 65 years or older (genotype: χ(2) = 8.39, df = 2, P = 0.015; allele: χ2 = 9.13, df = 1, P = 0.003, odd ratio (OR) = 1.91, 95% confidential interval (CI) = 1.25 - 2.91). A break down analysis by gender shows that rs1746048 is likely a CHD risk factor under the recessive model in males (CC+CT versus TT: P = 0.05, χ(2) = 3.59, df = 1, OR = 1.72, 95% CI = 1.00 - 3.04). In addition, a meta-analysis of ten studies among over 107,000 individuals confirms that rs1746048 is a risk factor of CHD (P < 0.0001, OR = 1.12, 95% CI =1.09 - 1.15) and this agrees with the findings of our case-control study in Han Chinese.
Gene 03/2013; · 2.34 Impact Factor
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Limin Xu,
Jianqing Zhou,
Stephanie Huang,
Yi Huang,
Yanping LE,
Danjie Jiang,
Feiming Wang,
Xi Yang,
Weifeng Xu,
Xiaoyan Huang,
Changzheng Dong,
Lina Zhang,
Meng Ye,
Jiangfang Lian, Shiwei Duan
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ABSTRACT: Previous genome-wide association studies (GWAS) have revealed seven single nucleotide polymorphisms (SNPs) that affect lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) activity or levels in American and European individuals. A total of 290 coronary heart disease (CHD) patients, 198 non-CHD patients and 331 unrelated healthy volunteers were recruited for the present case-control study of Han Chinese. Four SNPs (rs964184 of ZNF259, rs7528419 of CELSR2 and rs7756935 and rs1805017 of PLA2G7) were shown to be significantly associated with CHD. The rs964184-G allele of the ZNF259 gene was identified as a risk factor of CHD in females (odds ratio (OR) =1.49, 95% confidence interval (CI) =1.00-2.22, P=0.05). The rs7528419-G allele of the CELSR2 gene was protective against CHD in males (OR=0.48, 95% CI=0.25-0.93, P=0.04). The other two alleles (rs7756935-C and rs1805017-A) of the PLA2G7 gene acted as protective factors against CHD in females (rs7756935-C: OR=0.59, 95% CI=0.35-1.00, P=0.05; rs1805017-A: OR=0.51, 95% CI=0.28-0.93, P=0.03). Moreover, rs1805017 of the PLA2G7 gene was associated with the severity of CHD only in females (r(2)=0.02, P=0.04). We identified four Lp-PLA(2)-associated SNPs significantly associated with CHD in a Han Chinese population. Specifically, rs7528419 was protective factor against CHD in males, while the other two SNPs (rs7756935 and rs1805017 of the PLA2G7 gene) were protective factors against CHD in females and rs964184 of the ZNF259 gene was regarded as a risk factor for CHD in females.
Experimental and therapeutic medicine 03/2013; 5(3):742-750.
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Lina Zhang,
Fang Yuan,
Panpan Liu,
Lijuan Fei,
Yi Huang,
Limin Xu,
Lingmei Hao,
Xujun Qiu,
Yanping Le,
Xi Yang,
Weifeng Xu,
Xiaoyan Huang,
Meng Ye,
Jianqing Zhou,
Jiangfang Lian, Shiwei Duan
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ABSTRACT: OBJECTIVE: To explore the association of rs11206510 (PCSK9 gene) and rs1122608 (LDLR gene) polymorphisms with coronary heart disease (CHD) in Han Chinese. METHODS: A total of 813 participants (290 CHD cases, 193 non-CHD controls and 330 healthy controls) were recruited in the case-control study. DNA genotyping was performed on the SEQUENOM® Mass-ARRAY iPLEX® platform. χ(2)-test was used to compare the genotype distribution and allele frequencies. Two meta-analyses were performed to establish the association between the two polymorphisms with CHD. RESULTS: No significant associations between the two SNPs and the risk of CHD were observed in the present study. The meta-analysis of rs11206510 of PCSK9 gene comprises 11 case-control studies with a total of 69,054 participants. Significant heterogeneity was observed in Caucasian population in subgroup analysis of the association studies of rs11206510 with CHD (P = 0.003, I(2) = 67.2%). The meta-analysis of LDLR gene rs1122608 polymorphism comprises 7 case-control studies with a total of 20,456 participants and the heterogeneity of seven studies was minimal (P = 0.148, I(2) = 36.7%). CONCLUSION: The results of the meta-analyses indicated that both SNPs were associated with CHD in Caucasians (P < 0.05) but not in Asians. The results from our case-control study and meta-analyses might be explained by genetic heterogeneity in the susceptibility of CHD and ethnic differences between Asians and Caucasians.
Clinical biochemistry 02/2013; · 2.02 Impact Factor
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Jiangfang Lian,
Yi Huang,
R Stephanie Huang,
Limin Xu,
Yanping Le,
Xi Yang,
Weifeng Xu,
Xiaoyan Huang,
Meng Ye,
Jianqing Zhou, Shiwei Duan
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ABSTRACT: The goal of our study is to assess the contribution of four eosinophil related gene variants (rs12619285, rs1420101, rs3184504 and rs4143832) to the risk of coronary heart disease (CHD). We conducted four meta-analyses of studies examining the association between four eosinophil related gene variants and the risk of CHD. A systematic search was conducted using MEDLINE, EMBASE, Web of Science and China National Knowledge Infrastructure (CNKI), Wanfang Chinese Periodical. A case-control study was conducted between 162 CHD cases and 119 non-CHD controls to explore their contribution to CHD. For rs3184504 of SH2B3 gene, the meta-analysis was performed among 19 study stages among 94,555 participants. Significant association between rs3184504 and CHD risk was observed in European and South Asian populations (OR = 1.13, 95 % CI = 1.10-1.16, p < 0.0001, fixed-effect method). For the other SNPs (rs12619285, rs1420101, and rs4143832), we combined our case-control data with the previous studies and found no association of them with the risk of CHD. No significant contribution of the four genetic variants to CHD was observed in Han Chinese (p > 0.05). In conclusion, our results supported a significant association between rs3184504 of SH2B3 gene and the risk of CHD in Europeans and South Asians, although we were unable to observe association between the four variants and the risk of CHD in Han Chinese.
Journal of Thrombosis and Thrombolysis 01/2013; · 1.48 Impact Factor
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Danjie Jiang,
Dawei Zheng,
Lingyan Wang,
Yi Huang,
Haibo Liu,
Leiting Xu,
Qi Liao,
Panpan Liu,
Xinbao Shi,
Zhaoyang Wang,
Lebo Sun,
Qingyun Zhou,
Ni Li,
Limin Xu,
Yanping Le,
Meng Ye,
Guofeng Shao, Shiwei Duan
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ABSTRACT: PLA2G7 gene product is a secreted enzyme whose activity is associated with coronary heart disease (CHD). The goal of our study is to investigate the contribution of PLA2G7 promoter DNA methylation to the risk of CHD. Using the bisulphite pyrosequencing technology, PLA2G7 methylation was measured among 36 CHD cases and 36 well-matched controls. Our results indicated that there was a significant association between PLA2G7 methylation and CHD (adjusted P = 0.025). Significant gender-specific correlation was observed between age and PLA2G7 methylation (males: adjusted r = -0.365, adjusted P = 0.037; females: adjusted r = 0.373, adjusted P = 0.035). A breakdown analysis by gender showed that PLA2G7 methylation was significantly associated with CHD in females (adjusted P = 0.003) but not in males. A further two-way ANOVA analysis showed there was a significant interaction between gender and status of CHD for PLA2G7 methylation (gender*CHD: P = 6.04E-7). Moreover, PLA2G7 methylation is associated with the levels of total cholesterols (TC, r = 0.462, P = 0.009), triglyceride (TG, r = 0.414, P = 0.02) and Apolipoprotein B (ApoB, r = 0.396, P = 0.028) in females but not in males (adjusted P>0.4). Receiver operating characteristic (ROC) curves showed that PLA2G7 methylation could predict the risk of CHD in females (area under curve (AUC) = 0.912, P = 2.40E-5). Our results suggest that PLA2G7 methylation changes with aging in a gender-specific pattern. The correlation between PLA2G7 methylation and CHD risk in females is independent of other parameters including age, smoking, diabetes and hypertension. PLA2G7 methylation might exert its effects on the risk of CHD by regulating the levels of TC, TG, and ApoB in females. The gender disparities in the PLA2G7 methylation may play a role in the molecular mechanisms underlying the pathophysiology of CHD.
PLoS ONE 01/2013; 8(3):e59752. · 4.09 Impact Factor
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Yi Huang,
Jiangfang Lian,
R Stephanie Huang,
Feiming Wang,
Limin Xu,
Yanping Le,
Xi Yang,
Weifeng Xu,
Xiaoyan Huang,
Meng Ye,
Jianqing Zhou, Shiwei Duan
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ABSTRACT: Westaway et al. have revealed a significant association between common variants of calsequestrin-2 (CASQ2) and nitric oxide synthase 1 (neuronal) adaptor protein (NOS1AP) and the risk of sudden death in patients of coronary heart disease (CHD). In light of the findings, we aim to explore the association between variants of the two genes and CHD risk in Han Chinese. Our results show a significant contribution of rs10918859 of the NOS1AP gene to CHD in Han Chinese (genotype: χ(2)=8.33, df=2, p=0.015; allele: χ(2)=4.00, df=1, p=0.047, odds ratio [OR]=1.44, 95% confidence interval [CI]=1.00-2.05). The association of rs10918859 with CHD is seen only in men (genotype: χ(2)=7.81, df=2, p=0.02; allele: χ(2)=4.49, df=1, p=0.03, OR=1.66, 95% CI=1.03-2.66). Moreover, rs10918859 is likely to exert its effect under a dominant model in men (χ(2)=7.6, df=1, p=0.005, OR=2.46, 95% CI=1.29-4.71). No association is observed between CASQ2 variants and CHD risk. The frequencies of rs12084280-C and rs10918859-A are higher in Han Chinese (36.7% and 41.6%) than those in Europeans (11% and 19.4%, respectively). These ethnic differences imply that further validation of NOS1AP in the susceptibility of CHD in other populations is warranted. We confirm that rs10918859 of the NOS1AP gene is associated with CHD in Han Chinese. In addition, here we report a gender effect in the association between rs10918859 of the NOS1AP gene and CHD.
Genetic Testing and Molecular Biomarkers 11/2012; · 1.11 Impact Factor
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Jianqing Zhou,
Yi Huang,
R Stephanie Huang,
Feiming Wang,
Limin Xu,
Yanping Le,
Xi Yang,
Weifeng Xu,
Xiaoyan Huang,
Jiangfang Lian, Shiwei Duan
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ABSTRACT: Peden et al. have revealed a significant association between four new risk loci and coronary heart disease (CHD) in Europeans and South Asians. The goal of this study is to evaluate the contribution of these genetic loci to CHD risk in Han Chinese.
We recruited 161 CHD patients and 112 controls proved by angiography originated from Ningbo in the Eastern China, and performed a case-control association study of the four significant SNPs.
Among the four tested SNPs, we found a significant association of rs974819 in PDGFD gene with CHD (allele p=0.04; OR=1.45, 95% CI=1.02 - 2.08) and the allele A/G of rs974819 shows significant difference in females (allele p=0.04; OR=1.83, 95% CI=1.01 - 3.31). A further meta-analysis showed that rs974819 of PDGFD gene was significantly associated with an increasing risk of CHD (OR=1.08, 95% CI=1.05 - 1.11) in both Europeans and South Asians including Han Chinese.
Our findings suggests that rs974819 of PDGFD is also a CHD risk factor in Han Chinese. In addition, it presents a sex-dependent genetic effect.
Thrombosis Research 06/2012; 130(4):602-6. · 2.44 Impact Factor
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Ping Peng,
Jiangfang Lian,
R Stephanie Huang,
Limin Xu,
Yi Huang,
Yanna Ba,
Xi Yang,
Xiaoyan Huang,
Changzhen Dong,
Lina Zhang,
Meng Ye,
Jianqing Zhou, Shiwei Duan
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ABSTRACT: The goal of our study is to assess the contribution of KIF6 Trp719Arg to both the risk of CHD and the efficacy of statin therapy in CHD patients.
Meta-analysis of 8 prospective studies among 77,400 Caucasians provides evidence that 719Arg increases the risk of CHD (P<0.001, HR = 1.27, 95% CI = 1.15-1.41). However, another meta-analysis of 7 case-control studies among 65,200 individuals fails to find a significant relationship between Trp719Arg and the risk of CHD (P = 0.642, OR = 1.02, 95% CI = 0.95-1.08). This suggests that the contribution of Trp719Arg to CHD varies in different ethnic groups. Additional meta-analysis also shows that statin therapy only benefit the vascular patients carry 719Arg allele (P<0.001, relative ratio (RR) = 0.60, 95% CI = 0.54-0.67). To examine the role of this genetic variant in CHD risk in Han Chinese, we have conducted a case-control study with 289 CHD cases, 193 non-CHD controls, and 329 unrelated healthy volunteers as healthy controls. On post hoc analysis, significant allele frequency difference of 719Arg is observed between female CHD cases and female total controls under the dominant model (P = 0.04, χ(2) = 4.228, df = 1, odd ratio (OR) = 1.979, 95% confidence interval (CI) = 1.023-3.828). Similar trends are observed for post hoc analysis between female CHD cases and female healthy controls (dominant model: P = 0.04, χ(2) = 4.231, df = 1, OR = 2.015, 95% CI = 1.024-3.964). Non-genetic CHD risk factors are not controlled in these analyses.
Our meta-analysis demonstrates the role of Trp719Arg of KIF6 gene in the risk of CHD in Caucasians. The meta-analysis also suggests the role of this variant in statin therapeutic response in vascular diseases. Our case-control study suggests that Trp719Arg of KIF6 gene is associated with CHD in female Han Chinese through a post hoc analysis.
PLoS ONE 01/2012; 7(12):e50126. · 4.09 Impact Factor
