Incidence of genetic polymorphisms involved in lipid metabolism among Chinese patients with osteonecrosis of the femoral head

Abstract Background Genetic polymorphisms of key proteins involved in clopidogrel absorption, metabolism, and action may contribute to variability in platelet inhibition in patients undergoing percutaneous coronary intervention (PCI), but their impacts on cardiovascular outcomes remain unclear. Purpose To examine the associations between genetic polymorphisms and cardiovascular outcomes in Chinese patients undergoing PCI and treated with clopidogrel and aspirin. Methods This prospective cohort study consecutively enrolled 2,453 post-PCI patients treated with clopidogrel and aspirin. Adenosine diphosphate-induced platelet aggregation was measured by light transmission aggregometry. A total of 40 single nucleotide polymorphisms (SNPs) of 18 genes selected according to published studies were investigated using an improved multiplex ligation detection reaction technique. The primary outcome was major adverse cardiovascular event (MACE), the composite of cardiovascular death, non-fatal myocardial infarction (MI), and ischemic stroke within one year after PCI. Results We restricted the analyses to the first 1,452 patients who had finished one-year follow-up and complete data on genotyping and platelet aggregation. 44 (3.03%) patients suffered MACE. Among the 40 SNPs, only the A-allele carriers of CYP2C19*2 had a significant higher risk of MACE (adjusted HR 2.05; 95% CI, 1.01–4.19; p=0.048) and platelet aggregation than non-A-carriers after adjusting age, sex, MI presentation, and left ventricular ejection fraction. CYP2C19*3, CYP2B6 rs3745274, and PEAR1 rs12041331 variants were also significantly associated with platelet aggregation (all p<0.05) but not with MACE at 1 year. Conclusion About 54.2% of Chinese patients with PCI were A-allele carriers of CYP2C19*2, who face a two-fold higher risk of MACE than non-A-allele carriers in Chinese patients after PCI. It would help identify low clopidogrel responders and optimize antiplatelet therapy before drug administration. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Natural Science Funding of China

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Effects of SCN1A and GABA Receptor Genetic Polymorphisms on Carbamazepine Tolerability and Efficacy in Chinese Patients with Partial Seizures: 2‐Year Longitudinal Clinical Follow‐Up

CNS Neuroscience & Therapeutics ◽

10.1111/j.1755-5949.2012.00321.x ◽

2012 ◽

Vol 18 (7) ◽

pp. 566-572 ◽

Cited By ~ 30

Author(s):

Bo‐Ting Zhou ◽

Qiu‐Hong Zhou ◽

Ji‐Ye Yin ◽

Guo‐Liang Li ◽

Jian Qu ◽

...

Keyword(s):

Genetic Polymorphisms ◽

Gaba Receptor ◽

Chinese Patients ◽

Partial Seizures

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Association of SREBP2 gene polymorphisms with the risk of osteonecrosis of the femoral head relates to gene expression and lipid metabolism disorders

Molecular Medicine Reports ◽

10.3892/mmr.2017.7473 ◽

2017 ◽

Vol 16 (5) ◽

pp. 7145-7153 ◽

Cited By ~ 4

Author(s):

Yang Song ◽

Zhenwu Du ◽

Bingpeng Chen ◽

Ming Ren ◽

Qiwei Yang ◽

...

Keyword(s):

Gene Expression ◽

Lipid Metabolism ◽

Femoral Head ◽

Gene Polymorphisms ◽

Lipid Metabolism Disorders

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Lack of effect of genetic polymorphisms of SLCO1B1 on the lipid-lowering response to pitavastatin in Chinese patients

Acta Pharmacologica Sinica ◽

10.1038/aps.2009.203 ◽

2010 ◽

Vol 31 (3) ◽

pp. 382-386 ◽

Cited By ~ 16

Author(s):

Guo-ping Yang ◽

Hong Yuan ◽

Bin Tang ◽

Wei Zhang ◽

Lian-sheng Wang ◽

...

Keyword(s):

Genetic Polymorphisms ◽

Chinese Patients ◽

Lipid Lowering

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Associations between Common Genetic Polymorphisms in Angiopoietin-Like Proteins 3 and 4 and Lipid Metabolism and Adiposity in European Adolescents and Adults

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2009-0769 ◽

2009 ◽

Vol 94 (12) ◽

pp. 5070-5077 ◽

Cited By ~ 20

Author(s):

Vanessa Legry ◽

Szilvia Bokor ◽

Dominique Cottel ◽

Laurent Beghin ◽

Giovina Catasta ◽

...

Keyword(s):

Lipid Metabolism ◽

Allele Frequency ◽

Genetic Polymorphisms ◽

Body Fat ◽

Minor Allele Frequency ◽

Cholesterol Metabolism ◽

Hdl Cholesterol ◽

Minor Allele ◽

Peroxisome Proliferator ◽

Independent Population

Context: Plasma-borne angiopoietin-like proteins (ANGPTL) act as endocrine factors on their target tissues. Because ANGPTL3 and ANGPTL4 play important roles in lipid metabolism and the regulation of adiposity in mice, we hypothesized that genetic variability at the ANGPTL3 and ANGPTL4 genes loci might influence lipid metabolism and fat deposition in humans. Objective: The aim of the study was to examine the association between ANGPTL3 and ANGPTL4 genetic polymorphisms and metabolic phenotypes in adolescent and adult samples. Design and Participants: Two independent population-based studies, one composed of 1144 adolescents (mean age, 14.8 ± 1.4 yr) from nine European countries (the HELENA study) and the other composed of 1155 adults (age range, 35–65 yr) from Northern France (the MONICA Lille study), were genotyped for one ANGPTL3 polymorphism and four ANGPTL4 polymorphisms. Results: The ANGPTL3 rs11207997 polymorphism (minor allele frequency, 0.32) was associated with lower plasma HDL-cholesterol and apolipoprotein A-I levels in both adolescents (P = 0.0004, P = 0.00006, respectively) and adults (P = 0.03, P = 0.02, respectively). The ANGPTL4 rs4076317 polymorphism (minor allele frequency, 0.29) was associated with a higher percentage of body fat (P = 0.02) in adolescents and a higher waist-to-hip ratio (in interaction with the peroxisome proliferator-activated receptor γ Pro12Ala polymorphism) in adults (P = 0.0004). Conclusion: The present study underlines the role of ANGPTL3 in HDL-cholesterol metabolism as early as in adolescence. Our data also suggest possible associations between ANGPTL4 polymorphisms and body fat, but these findings require replication.

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