Associations of <i>MTHFR</i> and <i>MTRR</i> Polymorphisms With Serum Lipid Levels in Chinese Hypertensive Patients

Jiang, Shanqun; Zhao, Ruimeng; Pan, Mingluo; Venners, Scott A.; Zhong, Guisheng; Hsu, Yi‐Hsiang

doi:10.1177/1076029612467226

Cited by 26 publications

(35 citation statements)

References 35 publications

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“…It can cause an alanine to valine substitution at position 222 of the enzyme, creating a thermolabile enzyme [6], and has been related to elevated plasma Hcy concentration [9]. Our previous [16,17] and present studies consistently demonstrated that individuals with the 677TT genotype had significantly higher TC and LDL-C levels than those with the 677CC + CT genotypes in a Chinese hypertensive or general population. Yilmaz et al [10] and Zhang et al [18] have reported that carriers of the 677T allele have significantly higher TC and LDL-C than 677T allele non-carriers.…”

Section: Discussionsupporting

confidence: 63%

“…Our previous studies [16,17] examined the effects of Hcy metabolic gene polymorphisms and their interactions with environmental factors on serum lipid levels, leading us to conclude that both the MTHFR and MTRR gene polymorphisms could be important genetic determinants of serum lipid levels dependent on environmental factors, including Hcy, gender, alcohol consumption, and smoking status, in patients with hypertension. In order to confirm and better generalize these findings, we further investigated the effects of the Hcy metabolic gene polymorphisms and their interactions with gender on serum lipid levels in this study's relatively larger general population from distinct geographic regions.…”

Section: Discussionmentioning

confidence: 99%

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WITHDRAWN: Association of homocysteine-metabolizing enzyme gene polymorphisms and lipid profiles: an investigation of a geneenvironment interaction

Jiang¹,

Venners²,

Hsu³

et al. 2018

Oncotarget

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The interaction term for the MTHFR 677TT genotype and gender was also significant for TC and LDL-C levels (P = 0.0147 and 0.0243 for interaction, respectively). Further haplotype analysis showed that there also were significant interactions between gender and hap2 (MTHFR 677C/1298A) on TC (P = 0.009) and LDL-C (P = 0.013). We suggest that the negative effects of the MTR and MTHFR genotypes on serum lipids are based on certain gene-environment interactions in the Chinese general population.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Association of homocysteine-metabolizing enzyme gene polymorphisms and lipid profiles: an investigation of a geneenvironment interaction

Jiang¹,

Venners²,

Hsu³

et al. 2018

Oncotarget

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“…Such patients are very susceptible to developing dementia. Thus, studies that evaluated the relationship between antihypertension treatment and dementia have yielded inconsistent results (Bautista, 2006;Shantha et al, 2009;Jiang et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Disrupted Frontoparietal Network Mediates White Matter Structure Dysfunction Associated with Cognitive Decline in Hypertension Patients

Liang

Chen

et al. 2015

Journal of Neuroscience

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Some previous reports have suggested that hypertension is a risk factor for dementia and cognitive impairments. Using behavioral data from 1007 elderly human subjects (405 hypertensive patients) of Han ethnicity from Beijing, China, the present study aimed to assess the effects of hypertension on cognitive performance and explore related neuronal changes via advanced resting-state functional magnetic resonance imaging and diffusion tensor imaging data from 84 of these subjects (44 hypertensive patients). Cognitively, we found that patients with hypertension showed decreased executive functions and attention compared with those with normotension in the large sample. In magnetic resonance imaging scan sample, using independent component analysis to examine the functional connectivity difference between the two groups, we found that the frontoparietal networks in the hypertensive group exhibited altered patterns compared with the control group, mainly in the inferior parietal lobe, left inferior frontal lobe, and precuneus. Using tract-based spatial statistics to investigate the between-group structural difference, we found that the hypertensive group showed significantly reduced integrity of white matter in the bilateral superior longitudinal fasciculus. Importantly, using the mediation analysis, we found that the functional connectivity of the frontoparietal networks mediates the impact of white matter on executive function in the hypertensive group. The results demonstrate that hypertension targets a specific pattern of cognitive decline, possibly due to deficits in the white matter and functional connectivity in frontal and parietal lobes. Our findings highlight the importance of brain protection in hypertension.

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“…Previous studies indicated that methylenetetrahydrofolate reductase ( MTHFR ) C677T and methionine synthase reductase ( MTRR ) A66G polymorphisms are significantly associated with serum lipid levels [8–11]. MTHFR catalyzes the reduction of methylenetetrahydrofolate to methyltetrahydrofolate, a key methyl donor for homocysteine remethylation to methionine [12].…”

Section: Introductionmentioning

confidence: 99%

“…However, the underlying mechanism is unclear. Despite some advances in the identification of sex-specific genetic association with plasma lipid levels [11, 32, 33], few studies have explored the modifying effects of sex in the interactions between single nucleotide polymorphisms (SNPs) and overweight/obesity on lipid concentrations. Such exploration may provide valuable insight into the factors causing gender difference in the plasma lipid profile.…”

Section: Introductionmentioning

confidence: 99%

Gender-specific interactions of MTHFR C677T and MTRR A66G polymorphisms with overweight/obesity on serum lipid levels in a Chinese Han population

et al. 2016

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BackgroundLittle is known regarding the interactions of methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G polymorphisms with overweight/obesity on serum lipid profiles. The aim of the current study was to explore interactions between the two polymorphisms and overweight/obesity on four common lipid levels in a Chinese Han population and further to evaluate whether these interactions exhibit gender-specificity.MethodsA total of 2239 participants (750 females and 1489 males) were enrolled into this study. The genotypes of the MTHFR C677T and MTRR A66G were determined by a TaqMan assay. Overweight and obesity were defined as a body mass index between 24 and 27.99 and ≥ 28 kg/m2, respectively. The interactions were examined by factorial design covariance analysis, and further multiple comparisons were conducted by Bonferroni correction.ResultsThere was no significant difference in the genotypic and allelic frequencies between females and males (MTHFR 677 T allele: 54.47 % for females and 54.40 % for males; MTRR 66G allele: 24.73 % for females and 24.71 % for males). Interaction between the MTHFR C677T polymorphism and overweight/obesity on serum triglyceride levels, and interaction between the MTRR A66G polymorphism and overweight/obesity on serum high-density lipoprotein cholesterol levels were detected in women (P = 0.015 and P = 0.056, respectively). For female subjects with overweight/obesity, the serum triglyceride levels in MTHFR 677TT genotype [1.09 (0.78–1.50) mmol/L] were significantly higher as compared with MTHFR 677CC genotype [0.90 (0.60–1.15) mmol/L, P = 0.007], and the MTRR 66GG genotype carriers had higher serum high-density lipoprotein cholesterol levels than those with MTRR 66AG genotype (1.46 ± 0.50 vs. 1.19 ± 0.31 mmol/L, P = 0.058). Furthermore, in male subjects with overweight/obesity, the MTHFR 677CT genotype carriers had higher low-density lipoprotein cholesterol levels than those with MTHFR 677TT genotype (2.96 ± 1.07 vs. 2.74 ± 0.88 mmol/L, P = 0.015).ConclusionsOur results indicate that there exist interactive effects of the MTHFR C677T and MTRR A66G polymorphisms with overweight/obesity on some lipid traits in Chinese Han population, and the effects were gender-specific.

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Associations of MTHFR and MTRR Polymorphisms With Serum Lipid Levels in Chinese Hypertensive Patients

Abstract: Both MTHFR and MTRR gene polymorphisms could be important genetic determinants of serum lipid levels in Chinese patients with hypertension. These findings need to be replicated in a larger sample.

Cited by 26 publications

References 35 publications

WITHDRAWN: Association of homocysteine-metabolizing enzyme gene polymorphisms and lipid profiles: an investigation of a geneenvironment interaction

WITHDRAWN: Association of homocysteine-metabolizing enzyme gene polymorphisms and lipid profiles: an investigation of a geneenvironment interaction

Disrupted Frontoparietal Network Mediates White Matter Structure Dysfunction Associated with Cognitive Decline in Hypertension Patients

Gender-specific interactions of MTHFR C677T and MTRR A66G polymorphisms with overweight/obesity on serum lipid levels in a Chinese Han population

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