Common polymorphisms in ITGA2, PON1 and THBS2 are associated with coronary atherosclerosis in a candidate gene association study of the Chinese Han population

Wang, Ying; Fu, Wenqing; Xie, Fang; Wang, Yi; Chu, Xun; Wang, Haifeng; Shen, Min; Sun, Weiwei; Rong, Lei; Yang, Lin; Wu, Hong; Foo, Jia Nee; Liu, Jing; Li, Jin; Huang, Wei

doi:10.1038/jhg.2010.53

Cited by 23 publications

(17 citation statements)

References 30 publications

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“…Previous studies offer insights into the observed associations. For example, common polymorphisms in ITGA2 (an ITGA7 homolog) were associated with coronary atherosclerosis in a candidate gene association study of the Chinese Han population (36). Variants in CEP164 and CEP68, which are homologs of CEP72, were reported to be associated with TG and LDL-C fasting levels (5, 21, 37).…”

Section: Discussionmentioning

confidence: 99%

An exome-wide sequencing study of lipid response to high-fat meal and fenofibrate in Caucasians from the GOLDN cohort

Geng

Irvin

Hidalgo

et al. 2018

Journal of Lipid Research

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Our understanding of genetic influences on the response of lipids to specific interventions is limited. In this study, we sought to elucidate effects of rare genetic variants on lipid response to a high-fat meal challenge and fenofibrate (FFB) therapy in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) cohort using an exome-wide sequencing-based association study. Our results showed that the rare coding variants in ITGA7, SIPA1L2, and CEP72 are significantly associated with fasting low-density lipoprotein cholesterol (LDL-C) response to FFB (P=1.24E-07), triglyceride postprandial area under the increase (AUI) (P=2.31E-06), and triglyceride postprandial AUI response to FFB (P=1.88E-06) respectively. We sought to replicate the association for SIPA1L2 in the Heredity and Phenotype Intervention (HAPI) Heart Study, which included a high-fat meal challenge but not FFB treatment. The associated rare variants in GOLDN were not observed in the HAPI Heart study and thus the gene-based result was not replicated. For functional validation, we found gene transcript level of SIPA1L2 is associated with triglyceride postprandial AUI (P≤0.05) in GOLDN. Our study suggests unique genetic mechanisms contributing to the lipid response to the high-fat meal challenge and FFB therapy.

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Section: Discussionmentioning

confidence: 99%

An exome-wide sequencing study of lipid response to high-fat meal and fenofibrate in Caucasians from the GOLDN cohort

Geng

Irvin

Hidalgo

et al. 2018

Journal of Lipid Research

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“…Considering the potential role of PON1 in lipid transfer from LDL-C to HDL-C, it is likely that decreased serum PON1 activity is associated with the increased LDL-C in the olanzapine group. Interestingly, serum PON-1 activity is reported to be negatively correlated with serum LDL-C level 51,52. Furthermore, our finding of a positive correlation between serum PON1 activity and HDL-C level in the olanzapine group is of great interest.…”

Section: Discussionmentioning

confidence: 58%

Reduced serum paraoxonase 1 (PON1) activity in patients with schizophrenia treated with olanzapine but not quetiapine

Ünsal¹,

Albayrak²,

Albayrak³

et al. 2013

NDT

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BackgroundSecond generation antipsychotics (SGAs) are currently the most prescribed drugs in the treatment of schizophrenia. Despite their advantages, which include greater improvement in negative symptoms, cognitive function, prevention of deterioration, quality of life, and fewer extrapyramidal symptoms, the concern regarding metabolic abnormalities which might cause cardiovascular diseases during treatment with SGAs have been rising. Paraoxonase 1 (PON1) is an enzyme mostly located on high-density lipoprotein particles, and has been shown to protect or inhibit lipoprotein oxidation. Growing evidence suggests that PON1 plays a key role in the pathophysiology of atherosclerosis.MethodsIn the present study, we measured serum PON1 activity and serum levels of total cholesterol (TC), triglyceride, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in patients with schizophrenia, who had been treated with either olanzapine or quetiapine, and in healthy controls. Thirty five patients who had been treated with olanzapine, 29 patients who had been treated with quetiapine, and 32 age, sex, and smoking status-matched healthy control (HC) participants were enrolled. Serum PON1 activity and serum levels of TC, triglyceride, HDL-C, and LDL-C were measured.ResultsSerum PON1 activity in the olanzapine group was significantly lower than that of HC and quetiapine groups. Furthermore, serum levels of TC and LDL-C in the olanzapine group were significantly higher than those of quetiapine and HC groups. Interestingly, there was a positive correlation between PON1 activity and HDL-C levels in the olanzapine group.ConclusionThese findings suggest that serum PON1 activity in patients treated with olanzapine was lower than that of HC and quetiapine groups, and that PON1 may play a role in the metabolic side effects associated with olanzapine treatment. A further study to examine the relationship between serum PON1 activity and cardiovascular and metabolic side effects during treatment with SGAs will be of great interest.

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“…Three studies (two European [10,33] and one Japanese [34]) were conducted without “proper” controls of no CHD history and were also excluded. One additional Chinese study met the inclusion criteria but was excluded due to unavailability of essential information even after contacting the authors [35]. The 9 remaining studies, together with PROCARDIS [25] and CARDIoGRAM [24] studies, were included in the meta-analysis (Table 1) [11,14,16,20-23,36,37].…”

Section: Resultsmentioning

confidence: 99%

TGFB1 genetic polymorphisms and coronary heart disease risk: a meta-analysis

Boer

Barsova

et al. 2012

BMC Med Genet

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BackgroundGenetic variations in TGFB1 gene have been studied in relation to coronary heart disease (CHD) risk, but the results were inconsistent.MethodsWe performed a systematic review of published studies on the potential role of TGFB1 genetic variation in CHD risk. Articles that reported the association of TGFB1 genetic variants with CHD as primary outcome were searched via Medline and HuGE Navigator through July 2011. The reference lists from included articles were also reviewed.ResultsData were available from 4 studies involving 1777 cases and 7172 controls for rs1800468, 7 studies involving 5935 cases and 10677 controls for rs1800469, 7 studies involving 6634 cases and 9620 controls for rs1982073, 5 studies involving 5452 cases and 9999 controls for rs1800471, and 4 studies involving 5143 cases and 4229 controls for rs1800472. The pooled odds ratios (ORs) for CHD among minor T allele carriers of rs1800469, minor C allele carriers of rs1982073, and minor C allele carriers of rs1800471 versus homozygous major allele carriers was 1.14 (95% confidence interval [CI]: 1.05-1.24), 1.18 (95% CI: 1.04-1.35), and 1.16 (95% CI: 1.02-1.32), respectively. No substantial heterogeneity for ORs was detected among the included Caucasian populations for all SNPs. However, for rs1800471, the statistical significance disappeared after adjusting for potential publication bias. No significant association was found between rs1800468 and rs1800472 variants and CHD risk.ConclusionMinor allele carriers of two genetic variants (rs1800469 and rs1982073) in TGFB1 have a 15% increased risk of CHD.

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Common polymorphisms in ITGA2, PON1 and THBS2 are associated with coronary atherosclerosis in a candidate gene association study of the Chinese Han population

Cited by 23 publications

References 30 publications

An exome-wide sequencing study of lipid response to high-fat meal and fenofibrate in Caucasians from the GOLDN cohort

An exome-wide sequencing study of lipid response to high-fat meal and fenofibrate in Caucasians from the GOLDN cohort

Reduced serum paraoxonase 1 (PON1) activity in patients with schizophrenia treated with olanzapine but not quetiapine

TGFB1 genetic polymorphisms and coronary heart disease risk: a meta-analysis

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