Associations between homocysteine metabolism related SNPs and carotid intima-media thickness: a Chinese sib pair study.
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.
Department of Epidemiology and Biostatistics, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.
Kexin
K
Sun
Department of Epidemiology and Biostatistics, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.
Jing
J
Song
Department of Epidemiology and Biostatistics, Capital Medical University, 10 You'anmenwai Xitoutiao, Beijing, 100069, China.
Kuo
K
Liu
Beijing Center for Disease Prevention and Control, No.16 He Pingli Middle Street, Dongcheng District, Beijing, 100013, China.
Kai
K
Fang
Pingshan New District Center for Disease Control and Prevention, Shenzhen, 518118, Guangdong, China.
Ling
L
Wang
Department of Epidemiology and Biostatistics, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.
Xueyin
X
Wang
Department of Epidemiology and Biostatistics, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.
Jing
J
Li
Department of Epidemiology and Biostatistics, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.
Xun
X
Tang
Department of Epidemiology and Biostatistics, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.
Yiqun
Y
Wu
Department of Epidemiology and Biostatistics, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.
Xueying
X
Qin
Department of Epidemiology and Biostatistics, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.
Tao
T
Wu
Department of Epidemiology and Biostatistics, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.
Pei
P
Gao
Department of Epidemiology and Biostatistics, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China.
Dafang
D
Chen
Department of Epidemiology and Biostatistics, Peking University Health Science Center, 38 Xueyuan Road, Beijing, 100191, China. yhhu@bjmu.edu.cn.
Yonghua
Y
Hu
D044466:Asian People; D050197:Atherosclerosis / Q000473:pathology; D017536:Carotid Artery, Common / Q000473:pathology; D059168:Carotid Intima-Media Thickness; D003324:Coronary Artery Disease / Q000235:genetics; D004843:Epistasis, Genetic; D005260:Female; D006710:Homocysteine / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D035781:Siblings
D006710:Homocysteine
Atherosclerosis; Carotid intima-media thickness; Gene–gene interaction; Homocysteine; Sib pair; Single nucleotide polymorphism