Association of CVD Candidate Gene Polymorphisms with Ischemic Stroke and Cerebral Hemorrhage in Chinese Individuals

Abstract

BackgroundContribution of cardiovascular disease related genetic risk factors for stroke are not clearly defined. We performed a genetic association study to assess the association of 56 previously characterized gene variants in 34 candidate genes from cardiovascular disease related biological pathways with ischemic stroke and cerebral hemorrhage in a Chinese population.MethodsThere were 1280 stroke patients (1101 with ischemic stroke and 179 with cerebral hemorrhage) and 1380 controls in the study. The genotypes for 56 polymorphisms of 34 candidate genes were determined by the immobilized probe approach and the associations of gene polymorphisms with ischemic stroke and cerebral hemorrhage were performed by logistic regression under an allelic model.ResultsAfter adjusting for age, sex, BMI and hypertension status by logistic regression analysis, we found that NPPA rs5063 was significantly associated with both ischemic stroke (odds ratio [OR] 0.69; 95% confidence interval [CI], 0.52 to 0.90; P = 0.006) and cerebral hemorrhage(OR = 0.39; 95%CI, 0.19 to 0.78; P = 0.007). In addition, MTHFR rs1801133 also was associated with cerebral hemorrhage (OR = 1.48; 95%CI, 1.16 to1.89; P = 0.001) but not with ischemic stroke (OR = 1.08; 95%CI, 0.96 to1.22; P = 0.210). After false discovery rate (FDR) correction, the association of NPPA rs5063 and MTHFR rs1801133 with cerebral hemorrhage remained significant.ConclusionsThe NPPA rs5063 is associated with reduced risk for cerebral hemorrhage and MTHFR rs1801133 is associated with increased risk of cerebral hemorrhage in a Chinese population.

Joint associations of folate, homocysteine and MTHFR, MTR and MTRR gene polymorphisms with dyslipidemia in a Chinese hypertensive population: a cross-sectional study

“…And MTRR restore oxidized cobalamin(II) to CH 3 -cobalamin(III) in order to maintain the activity of MTR [ 17 ]. MTHFR C677T (rs1801133) is a common mutation of MTHFR and its suggested being an unfavorable factor for cardiovascular diseases [ 19 , 20 ]. Yilmaz et al showed that the C allele has a protective effect on blood lipid concentration and the T allele has a harmful effect when they are screening MTHFR C677T polymorphism in renal transplant patients [ 21 ].…”

Peer Review #3 of "Single nucleotide polymorphism of MTHFR rs1801133 associated with elevated Hcy levels affects susceptibility to cerebral small vessel disease (v0.1)"

“…Compared to the CC genotype, the enzyme activity of the CT and TT genotypes is less than 35% and 70%, respectively (Frosst et al, 1995). The decreased enzyme activity eventually leads to the elevation of Hcy levels (Atadzhanov et al, 2013;Ou et al, 2014).…”

“…For the MTHFR gene, the cytosine (C) to thymine (T) substitution at position 677 (rs1801133) in the gene encoding region is the most common SNP. This variation leads to the conversion from alanine to valine at amino acid 222 (Jadavji et al, 2015), and is correlated with decrease of thermal stability of MTHFR and subsequent decrease of enzyme activity (Atadzhanov et al, 2013;Ou et al, 2014). Compared to the CC genotype, the enzyme activity of the CT and TT genotypes is less than 35% and 70%, respectively (Frosst et al, 1995).…”

Single nucleotide polymorphism of MTHFR rs1801133 associated with elevated Hcy levels affects susceptibility to cerebral small vessel disease

“…Compared to the CC genotype, the enzyme activity of the CT and TT genotypes is less than 35% and 70%, respectively (Frosst et al, 1995). The decreased enzyme activity eventually leads to the elevation of Hcy levels (Atadzhanov et al, 2013;Ou et al, 2014). In other words, the CT and TT genotypes are correlated with elevated Hcy levels through reducing the activity of MTHFR.…”

“…For the MTHFR gene, the cytosine (C) to thymine (T) substitution at position 677 ( rs1801133) in the gene encoding region is the most common SNP. This variation leads to the conversion from alanine to valine at amino acid 222 (Jadavji et al, 2015), and is correlated with decrease of thermal stability of MTHFR and subsequent decrease of enzyme activity (Atadzhanov et al, 2013;Ou et al, 2014). Compared to the CC genotype, the enzyme activity of the CT and TT genotypes is less than 35% and 70%, respectively (Frosst et al, 1995).…”