Identifying functional non-coding variants in APOA5/A4/C3/A1 gene cluster associated with coronary heart disease.
J Mol Cell Cardiol
; 144: 54-62, 2020 07.
Article
em En
| MEDLINE
| ID: mdl-32437778
ABSTRACT
Recent genome-wide association studies identified several polymorphisms in the APOA5/A4/C3/A1 gene cluster influencing lipids level and risk of coronary heart disease (CHD). However, few studies explored the molecular mechanism. The purposes of this study were to fine-map noncoding region between APOA1 and APOC3 and then explore the clinical relevance in CHD and potential underlying mechanisms. In this study, a 2.7-kb length of the non-coding region between APOA1 and APOC3 was screened and five polymorphisms were investigated in the case-control study. The molecular mechanism was explored. Our data confirmed the association between rs7123454, rs12721030, rs10750098, and rs12721028 with CHD in 828 patients and 828 controls and replicated it in an independent population of 405 patients and 405 controls. In addition, the rs10750098 and rs12721030 are significantly associated with decreased serum APOA1 levels (P = 4.2 × 10-4 and P = 3.2 × 10-5, combined analysis), while a significant association was observed between serum APOA1 level and CHD (OR 0.43, 95% CI 0.28-0.64, P < .01) with adjustment for clinical covariates and different population sets. In vitro evaluation of potential function of non-coding variants between APOA1 and APOC3 demonstrated that rs10750098 as being the most sufficient to confer the haplotype-specific effect on the regulation of APOs gene transcription. Our results strongly implicate the involvement of common noncoding DNA variants in APOA5/A4/C3/A1 gene cluster in the pathogenesis of dyslipidemia and the risk of CHD.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Apolipoproteínas A
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Família Multigênica
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Apolipoproteína A-I
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Doença das Coronárias
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RNA não Traduzido
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Apolipoproteína C-III
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Apolipoproteína A-V
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article