Associations of homocysteine status and homocysteine metabolism enzyme polymorphisms with hypertension and dyslipidemia in a Chinese hypertensive population

Yuan, Xiaojie; Wang, Tingcai; Gao, Jie; Wang, Yunchao; Chen, Yajun; Kaliannan, Kanakaraju; Li, Xiaochun; Xiao, Jing; Ma, Teng; Zhang, Lei; Shao, Zhongjun

doi:10.1080/10641963.2019.1571599

Cited by 22 publications

(16 citation statements)

References 39 publications

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“…In addition, HHcy increases the risk of hypertriglyceridemia [48,49]. Consistent with this, the serum triglyceride levels were high in the CBS-KO founder rabbits, and decreased signi cantly following betaine and vitamin B6 supplementation.…”

Section: Discussionsupporting

confidence: 64%

Hyperhomocysteinemia and Dyslipidemia in point mutation G307S of cystathionine β-synthase-deficient rabbit generated using CRISPR/Cas9

Zhang

Lü

Chen

et al. 2020

Preprint

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Background: Congenital hyper-homocysteinemia (HHcy) is caused by a defective cystathionine β-synthase (CBS) gene, and is frequently associated with dyslipdemia. The aim of this study was to further elucidate the effect of mutated CBS gene on circulating lipids using a rabbit model harboring a homozygous G307S point mutation in CBS.Methods: CRISPR/Cas9 system was used to edit the CBS gene in rabbit embryos. The founder rabbits were sequenced, and their plasma homocysteine (Hcy) and lipid profile were analyzed.Results: Six CBS-knockout (CBS-KO) founder lines with biallelic modifications were obtained. Mutation in CBS caused significant growth retardation and high mortality rates within 6 weeks after birth. In addition, the 6-week old CBS-KO rabbits showed higher plasma levels of Hcy, triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) compared to the age-matched wild-type (WT) controls. Histological analysis of the mutants showed accumulation of micro-vesicular cytoplasmic lipid droplets in the hepatocytes. However, gastric infusion of vitamin B and betaine complex significantly decreased the plasma levels of TG, TC and LDL-C in the CBS-KO rabbits, and alleviated hepatic steatosis compared to the untreated animals.Conclusion: A CBSG307S rabbit model was generated that exhibited severe dyslipidemia when fed on a normal diet, indicating that G307S mutation in the CBS gene is a causative factor for dyslipidemia.

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Section: Discussionsupporting

confidence: 64%

Hyperhomocysteinemia and Dyslipidemia in point mutation G307S of cystathionine β-synthase-deficient rabbit generated using CRISPR/Cas9

Zhang

Lü

Chen

et al. 2020

Preprint

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“…Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme reducing Hcy metabolism, which leads to HHcy [8,41]. The MTHFR 677 genotype, related to the serum concentration of Hcy [44], is characterized by the 677T allele and higher frequencies were found in north China [45]. Nutritional supplementation was another important factor.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Hyperhomocysteinemia in China: An Updated Meta-Analysis

Zeng

Yuan

et al. 2021

Biology

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We conducted a meta-analysis to systematically assess the prevalence of hyperhomocysteinemia (HHcy) in China, its change over time, and its determinants. Literature searches were conducted using English databases (PubMed, Embase, and Web of Science) and Chinese databases (CNKI, CBM, VIP, and Wanfang). The time ranges were from Jan 2014 to Mar 2021 in China. We adopted the random effects model to estimate the pooled positive rates of HHcy and corresponding 95% confidence intervals (95%CI). To find the sources of heterogeneity, we performed subgroup analysis and meta-regression. A total of 29 related articles were identified involving 338,660 participants with 128,147 HHcy cases. The estimated prevalence of HHcy in China was 37.2% (95%CI: 32.6–41.8%, I2 = 99.8%, p for heterogeneity < 0.001). The trend of HHcy prevalence was gradually upward over time, with increases during 2015–2016 (comparison to 2013–2014, p < 0.001), but steady between 2015–2016 and 2017–2018. Subgroup analysis showed that the prevalence was higher in the elderly over 55 years old, males, and residents in the north, inland, and rural China (for each comparison, p < 0.001). Meta-regression analysis revealed that age and area of study contributed to 42.3% of the heterogeneity between studies. The current meta-analysis provides strong evidence that the prevalence of HHcy is increasing in China, and varies substantially across different ages, genders, and geographic distribution. Accordingly, high-risk population groups should be focused on, and public health policies and strategies should be carried out to prevent and control HHcy in China.

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“…Studies show that HHcy is an independent risk factor for CVDs [3], which correlates positively with atherosclerotic symptoms induced by the high levels of TG, TC and LDL-C, and normal plasma HDL-C level [51,52]. In addition, HHcy increases the risk of hypertriglyceridemia [53,54]. Consistent with this, the serum triglyceride levels were high in the CBS-KO founder rabbits, and decreased signi cantly following betaine and vitamin B6 supplementation.…”

Section: Discussionmentioning

confidence: 64%

Hyperhomocysteinemia and Dyslipidemia in point mutation G307S of cystathionine β-synthase-deficient rabbit generated using CRISPR/Cas9

Zhang

Lü

Chen

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Congenital hyper-homocysteinemia (HHcy) is caused by a defective cystathionine β-synthase (CBS) gene, and is frequently associated with dyslipdemia. The aim of this study was to further elucidate the effect of mutated CBS gene on circulating lipids using a rabbit model harboring a homozygous G307S point mutation in CBS. Methods: CRISPR/Cas9 system was used to edit the CBS gene in rabbit embryos. The founder rabbits were sequenced, and their plasma homocysteine (Hcy) and lipid profile were analyzed. Results: Six CBS-knockout (CBS-KO) founder lines with biallelic modifications were obtained. Mutation in CBS caused significant growth retardation and high mortality rates within 6 weeks after birth. In addition, the 6-week old CBS-KO rabbits showed higher plasma levels of Hcy, triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) compared to the age-matched wild-type (WT) controls. Histological analysis of the mutants showed accumulation of micro-vesicular cytoplasmic lipid droplets in the hepatocytes. However, gastric infusion of vitamin B and betaine complex significantly decreased the plasma levels of TG, TC and LDL-C in the CBS-KO rabbits, and alleviated hepatic steatosis compared to the untreated animals. Conclusion: A CBSG307S rabbit model was generated that exhibited severe dyslipidemia when fed on a normal diet, indicating that G307S mutation in the CBS gene is a causative factor for dyslipidemia.

show abstract

Associations of homocysteine status and homocysteine metabolism enzyme polymorphisms with hypertension and dyslipidemia in a Chinese hypertensive population

Cited by 22 publications

References 39 publications

Hyperhomocysteinemia and Dyslipidemia in point mutation G307S of cystathionine β-synthase-deficient rabbit generated using CRISPR/Cas9

Hyperhomocysteinemia and Dyslipidemia in point mutation G307S of cystathionine β-synthase-deficient rabbit generated using CRISPR/Cas9

Prevalence of Hyperhomocysteinemia in China: An Updated Meta-Analysis

Hyperhomocysteinemia and Dyslipidemia in point mutation G307S of cystathionine β-synthase-deficient rabbit generated using CRISPR/Cas9

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