Hyperhomocysteinemia but Not the C677T Mutation of Methylenetetrahydrofolate Reductase Is an Independent Risk Determinant of Carotid Wall Thickening

McQuillan, Brendan; Beilby, John; Nidorf, Mark; Thompson, Peter L.; Hung, Joseph

doi:10.1161/01.cir.99.18.2383

Cited by 189 publications

(143 citation statements)

References 25 publications

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“…The finding of an interaction effect between smoking and MTHFR(C677T) genotype has not been reported previously. A suboptimal plasma folate status among smokers (Piyathilake et al, 1994;Cafolla et al, 2000;O'Callaghan et al, 2002) might explain the observed interaction, as plasma folate has been shown to interact with MTHFR(C677T) genotype (Jacques et al, 1996b;Brattstrom et al, 1998;Girelli et al, 1998;McQuillan et al, 1999;Dekou et al, 2001;Saw et al, 2001). The involvement of folate is further supported by another study in which smoking was reported to interact with the dietary intake of folate (De Bree et al, 2001b).…”

Section: Discussionmentioning

confidence: 99%

Effect of lifestyle factors on plasma total homocysteine concentrations in relation to MTHFR(C677T) genotype. Inter99 (7)

et al. 2004

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Objective: To examine the associations between various lifestyle factors-smoking habits, physical activity, dietary habits, coffee, tea, and alcohol consumption-and homocysteine (tHcy) in relation to MTHFR(C677T) genotype. Design: Cross-sectional population-based study. Setting: Residents of Copenhagen County, Denmark. Subjects: A random sample of 6457 men and women aged 30-60 years drawn from the Civil Registration System and invited to a health examination in 1999-2001. A total of 2788 participants were included in the statistical analysis. Main outcome measures: tHcy was measured using a Fluorescent Polarization Immuno Assay. MTHFR-genotype was determined by PCR and RFLP analysis. Information about lifestyle factors was obtained from a self-administered questionnaire. Results: Daily smoking, less healthy dietary habits, and coffee drinking were associated with elevated tHcy concentrations independent of other determinants. Wine consumption was related to tHcy in a J-shaped manner, whereas beer consumption was negatively associated with tHcy after multiple adjustments. Interaction was observed between smoking status and MTHFRgenotype, smoking status and sex, and beer consumption and age. The effect of smoking was more pronounced in persons with the TT genotype and in women. The effect of beer consumption was more pronounced at younger than at older ages. Conclusions: Smoking status, dietary habits, coffee intake, wine, and beer consumption were major lifestyle determinants of tHcy. Changes in these lifestyle factors may reduce tHcy concentrations, thereby lowering cardiovascular risk in the general population.

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Section: Discussionmentioning

confidence: 99%

Effect of lifestyle factors on plasma total homocysteine concentrations in relation to MTHFR(C677T) genotype. Inter99 (7)

et al. 2004

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“…Subjects were selected from two populations: the Carotid Ultrasound Disease Assessment Study (CUDAS) (19) and the Busselton Population Health Survey (20). These two populations were predominantly Caucasian and were collected from the same region of Western Australia.…”

Section: Methodsmentioning

confidence: 99%

A Pro12Ala polymorphism in the human peroxisome proliferator-activated receptor-gamma 2 is associated with combined hyperlipidaemia in obesity

Swarbrick

Chapman

McQuillan

et al. 2001

European Journal of Endocrinology

107

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Objective: Peroxisome proliferator-activated receptor-g2 (PPARg2) is an important regulator of adipose tissue metabolism and insulin sensitivity. The aim of this investigation was to determine whether a PPARg2 Pro12Ala polymorphism was associated with cardiovascular risk factors (obesity, blood pressure, diabetes and blood lipids) in Western Australian Caucasians n 663X Design: Subjects were selected from two population studies (the Carotid Ultrasound Disease Assessment Study (CUDAS) and Busselton Population Health Survey) on the basis of body mass index (BMI). 292 obese (BMI $30 kg/m 2 ) and 371 lean (BMI ,25 kg /m 2 ) subjects were studied. Methods: Blood pressure and anthropometric measurements were collected from all participants, as well as a fasting venous blood sample. Biochemical measurements (high-density lipoprotein (HDL)-and low-density lipoprotein-cholesterol, triglycerides) and PPARg2 Pro12Ala genotype were also determined. Results: Obese Pro/Ala and Ala/Ala subjects had lower levels of HDL-cholesterol P 0X032 and a trend towards higher levels of triglycerides P 0X055 compared with obese Pro/Pro subjects. In the obese group, the Ala allele was significantly associated with the presence of combined hyperlipidaemia (odds ratio 2.33, P 0X042X There was no significant difference in the frequency of the polymorphism between lean and obese groups P 0X069X No association was observed between Pro12Ala genotype and obesity, blood pressure or diabetes in either group. Conclusions: Obese carriers of the Pro12Ala polymorphism have a greater risk of developing combined hyperlipidaemia, possibly due to impaired activation of PPARg target genes. The Pro12Ala polymorphism is not directly associated with obesity, hypertension or diabetes in this population.

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“…26,27 In brief, this was a random electoral roll sample of 1111 predominantly Caucasian subjects aged 27-77, mean 53 years, from Perth, Western Australia, who were assessed for cardiovascular risk factors and had carotid B-mode ultrasound performed. The numbers of subjects were equally distributed between sexes and across each age decile.…”

Section: Study Populationmentioning

confidence: 99%

Circulating adiponectin levels associate with inflammatory markers, insulin resistance and metabolic syndrome independent of obesity

et al. 2008

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Background: Adiponectin is an abundantly expressed adipocyte-specific protein, whose level is decreased in obesity, and which appears to be a key participant in developing inflammation, insulin resistance and metabolic syndrome (MetS). We examined whether the relationship between adiponectin and inflammatory markers, insulin resistance and MetS was independent of obesity. Methods and results:The study was performed in 1094 men and women, aged 27-77 years, from a representative community population. We measured serum inflammatory markers, homoeostasis model assessment of insulin resistance (HOMA-IR) and prevalent MetS using National Cholesterol Education Program ATPIII criteria. Sex-and age-adjusted plasma adiponectin concentration was inversely correlated with body mass index (BMI), waist-hip ratio, diastolic blood pressure, triglycerides, glucose and fasting insulin, and positively correlated with HDL cholesterol (all Po0.005). Log plasma adiponectin was a significant negative correlate of the levels of C-reactive protein, interleukin-6, interleukin-18, fibrinogen and white cell count independent of level of obesity. Log plasma adiponectin was also an inverse associate of log HOMA-IR (Po0.001) independent of obesity. Subjects in the top compared to bottom sex-specific plasma adiponectin quartile had a multivariate-adjusted odds ratio (OR) of 0.21 (95% CI, 0.11-0.42; Po0.001) for prevalent MetS, and the association was independent of age, sex, BMI, log insulin and log intereukin-18 levels. Conclusion: Our findings suggest that higher circulating adiponectin levels may mitigate against adipose-related inflammation, insulin resistance and MetS as much in lean as obese persons. At any rate circulating adiponectin level is a strong risk marker for MetS, which is independent of measures of adiposity, insulin resistance and inflammatory markers.

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Hyperhomocysteinemia but Not the C677T Mutation of Methylenetetrahydrofolate Reductase Is an Independent Risk Determinant of Carotid Wall Thickening

Cited by 189 publications

References 25 publications

Effect of lifestyle factors on plasma total homocysteine concentrations in relation to MTHFR(C677T) genotype. Inter99 (7)

Effect of lifestyle factors on plasma total homocysteine concentrations in relation to MTHFR(C677T) genotype. Inter99 (7)

A Pro12Ala polymorphism in the human peroxisome proliferator-activated receptor-gamma 2 is associated with combined hyperlipidaemia in obesity

Circulating adiponectin levels associate with inflammatory markers, insulin resistance and metabolic syndrome independent of obesity

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