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Open Access 01-04-2017

Associations between homocysteine metabolism related SNPs and carotid intima-media thickness: a Chinese sib pair study

Authors: Kexin Sun, Jing Song, Kuo Liu, Kai Fang, Ling Wang, Xueyin Wang, Jing Li, Xun Tang, Yiqun Wu, Xueying Qin, Tao Wu, Pei Gao, Dafang Chen, Yonghua Hu

Published in: Journal of Thrombosis and Thrombolysis | Issue 3/2017

Abstract

Carotid intima-media thickness (CIMT) is a good surrogate for atherosclerosis. Hyperhomocysteinemia is an independent risk factor for cardiovascular diseases. We aim to investigate the relationships between homocysteine (Hcy) related biochemical indexes and CIMT, the associations between Hcy related SNPs and CIMT, as well as the potential gene–gene interactions. The present study recruited full siblings (186 eligible families with 424 individuals) with no history of cardiovascular events from a rural area of Beijing. We examined CIMT, intima-media thickness for common carotid artery (CCA-IMT) and carotid bifurcation, tested plasma levels for Hcy, vitamin B6 (VB6), vitamin B12 (VB12) and folic acid (FA), and genotyped 9 SNPs on MTHFR, MTR, MTRR, BHMT, SHMT1, CBS genes. Associations between SNPs and biochemical indexes and CIMT indexes were analyzed using family-based association test analysis. We used multi-level mixed-effects regression model to verify SNP-CIMT associations and to explore the potential gene–gene interactions. VB6, VB12 and FA were negatively correlated with CIMT indexes (p < 0.05). rs2851391 T allele was associated with decreased plasma VB12 levels (p = 0.036). In FABT, CBS rs2851391 was significantly associated with CCA-IMT (p = 0.021) and CIMT (p = 0.019). In multi-level mixed-effects regression model, CBS rs2851391 was positively significantly associated with CCA-IMT (Coef = 0.032, se = 0.009, raw p < 0.001) after Bonferoni correction (corrected α = 0.0056). Gene–gene interactions were found between CBS rs2851391 and BHMT rs10037045 for CCA-IMT (p = 0.011), as well as between CBS rs2851391 and MTR rs1805087 for CCA-IMT (p = 0.007) and CIMT (p = 0.022). Significant associations are found between Hcy metabolism related genetic polymorphisms, biochemical indexes and CIMT indexes. There are complex interactions between genetic polymorphisms for CCA-IMT and CIMT.

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Title: Associations between homocysteine metabolism related SNPs and carotid intima-media thickness: a Chinese sib pair study
Authors: Kexin Sun
Jing Song
Kuo Liu
Kai Fang
Ling Wang
Xueyin Wang
Jing Li
Xun Tang
Yiqun Wu
Xueying Qin
Tao Wu
Pei Gao
Dafang Chen
Yonghua Hu
Publication date: 01-04-2017
Publisher: Springer US
Published in: Journal of Thrombosis and Thrombolysis / Issue 3/2017
Print ISSN: 0929-5305
Electronic ISSN: 1573-742X
DOI: https://doi.org/10.1007/s11239-016-1449-x

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