Methylenetetrahydrofolate reductase C677T polymorphism is associated with central adiposity and increased androgenicity in healthy postmenopausal women

Lambrinoudaki, Ιrene; Kaparos, George; Papadimitriou, Dimitra; Sergentanis, Theodoros N.; Creatsa, Maria; Alexandrou, Andreas; Logothetis, E; Christodoulakos, George; Kouskouni, Evangelia

doi:10.1530/eje-07-0848

Cited by 16 publications

(22 citation statements)

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“…Postmenopause is associated with pro-atherogenic lipid profile, central adiposity, increased diastolic pressure and increased insulin resistance (1). Pro-atherogenic lipid profile is characterized in general with higher concentration of total cholesterol, LDL cholesterol, triglyceride and lipoprotein (a) (Lpa) (1,3). Furthermore, HDL cholesterol is maintained or decreased in postmenopausal women (4).…”

Section: Discussionmentioning

confidence: 99%

“…A postmenopause, a physiological state in the woman life, is associated with the increased risk for cardiovascular disease (1–3). Risk factors include an atherogenic lipid profile, small increases of systolic and diastolic blood pressure and increased sympathetic tone.…”

Section: Introductionmentioning

confidence: 99%

“…Risk factors include an atherogenic lipid profile, small increases of systolic and diastolic blood pressure and increased sympathetic tone. Furthermore, postmenopause is associated with central adiposity and increased insulin resistance (1,3). Among other, atherogenic lipid profile includes decreased or maintained level of high density lipoprotein (HDL) (1,3,4).…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, postmenopause is associated with central adiposity and increased insulin resistance (1,3). Among other, atherogenic lipid profile includes decreased or maintained level of high density lipoprotein (HDL) (1,3,4). Also, postmenopausal women show changes in the chemical composition of HDL, increased HDL oxidability and also decreased ability of HDL to prevent low density lipoprotein (LDL) oxidation (4).…”

Section: Introductionmentioning

confidence: 99%

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Paraoxonase 1 activity and phenotype distribution in premenopausal and postmenopausal women

Butorac

Ćelap

Kačkov³

et al. 2014

Biochem Med

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IntroductionPostmenopausal women have higher risk of cardiovascular disease. One of the contributing factors could be reduced activity of anti-atherogenic enzyme paraoxonase 1 (PON1). The aim of this study was to examine differences in the lipid status, paraoxonase and arylesterase PON1 activities and PON1 phenotype in women with regular menstrual cycle and in postmenopausal women.Materials and methods:The study included 51 women in reproductive age (25 in follicular and 26 in luteal phase of the menstrual cycle) and 23 women in postmenopause. Lipid parameters in sera were determined using original reagents and according to manufacturer protocol. PON1 activity in serum was assessed by spectrophotometric method with substrates: paraoxon and phenylacetate. PON1 phenotype was determined by double substrate method.Results:Compared to the women in follicular and luteal phase, postmenopausal women have significantly higher concentration of triglyceride [0.9 (0.7–1.3), 0.7 (0.6–1.0) vs. 1.5 (0.9–1.7) mmol/L; P = 0.002], cholesterol [5.10 (4.78–6.10), 5.05 (4.70–5.40) vs. 6.30 (5.73–7.23) mmol/L; P < 0.001], LDL [3.00 (2.56–3.63), 3.00 (2.70–3.70) vs. 3.90 (3.23–4.50) mmol/L; P < 0.001], and apolipoprotein B [0.88 (0.75–1.00), 0.79 (0.68–1.00) vs. 1.07 (0.90–1.24) mmol/L; P = 0.002]. PON1 basal [104 (66–260), 106 (63–250) vs. 93 (71–165) U/L; P = 0.847] and salt-stimulated paraoxonase activity [210 (131–462), 211 (120–442) vs. 180 (139–296) U/L; P = 0.857] as well as arylesterase activity [74 (63–82), 70 (54–91) vs. 70 (60–81) kU/L; P = 0.906] and PON1 phenotype (P = 0.810) were not different in the study groups.Conclusion:There are no differences in PON1 activity and PON1 phenotype between women with regular menstrual cycle and postmenopausal women.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Paraoxonase 1 activity and phenotype distribution in premenopausal and postmenopausal women

Butorac

Ćelap

Kačkov³

et al. 2014

Biochem Med

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“…It was reported that MTHFR Ala222Val polymorphism characterized individuals with metabolic obesity with normal weight; and is associated with elevated BMI and waist hip ratio in healthy postmenopausal women [29][30][31]. Previous researches could also elicit positive association of obesity and hypertension, coronary artery disease or liver diseases with MTH-FR C677T mutations [32][33][34].…”

Section: Discussionmentioning

confidence: 99%

Methylene Tetrahydrofolate Reductase and Angiotensin Converting Enzyme Gene Polymorphisms Related to Overweight/Obesity among Saudi Subjects from Qassim Region

et al. 2009

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Abstract.Background: This work was planned to check for the association of polymorphisms related to methylenetetrahydrofolate reductase (MTHFR) and angiotensin converting enzyme (ACE) genes with overweight/obesity among Saudi subjects from Qassim region. Methods: This work included 130 subjects having overweight or obesity and 111 normal controls. Their age mean ± SD was 27 ± 9.8 and 24 ± 8.8 years respectively. Their DNA was analyzed for polymorphisms of MTHFR; 677C/T and 1298 A/C and ACE; I/D genes using real-time PCR. Results: Genotype and allele frequencies of studied polymorphisms in cases of overweight/obesity showed no significant statistical difference compared to that of controls. However, on analysis of body mass index (BMI), cases showed slightly higher but statistically nonsignificant mean ± SD values among those carrying the mutant MTHFR 677 T allele (CT + TT vs. CC, 30.7 ± 4.5 vs. 29.9 ± 4.9), 1298 C allele (AC + CC vs. AA, 29.9 ± 4.1 vs. 29.7 ± 5.5) and ACE D allele (ID + DD vs. II, 30.0 ± 5.1 vs. 29.1 ± 2.8). In addition controls having the DD and ID genotypes showed higher statistically significant values of BMI than those of the II genotype (22.0 ± 1.9, 21.7 ± 2.6 and 19.5 ± 2.3 respectively, p < 0.05). Conclusion: There is no solid association of polymorphisms related to MTHFR and ACE genes with non-complicated overweight or obesity among Saudi subjects from Qassim Region.

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Apolipoprotein E (APOE) genotype regulates body weight and fatty acid utilization—Studies in gene‐targeted replacement mice

Huebbe

Dose

Schloesser

et al. 2014

Molecular Nutrition Food Res

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Apolipoprotein E (APOE), a constituent of lipoproteins, is suggested to have pleiotropic functions including regulation of adipocyte differentiation and food intake. Of the three human APOE alleles, the ɛ3 allele is most common, although it evolved from the ancestral APOE ɛ4. Evidence suggests that the worldwide distribution of the APOE ɛ3 allele may be a result of adaptive evolution, although the underlying reasons are not yet understood. In this study, we investigated whether the APOE ɛ3 allele may be associated with more efficient food conversion and fat storage and thus provide an advantage over the ɛ4 allele under certain conditions. Targeted replacement mice expressing the human APOE3 were heavier, ate more and exhibited a higher dietary energy yield compared to APOE4 mice. Fat mass and the expression of genes involved in triglyceride synthesis in adipose tissue were increased in APOE3 versus APOE4 animals, whereas leptin expression was lower, indicating reduced satiety. Energy expenditure was similar, but APOE3 mice spent more time running and covered longer running distances than APOE4 mice in running wheel experiments. Higher expression of Ucp and Fabp4 in skeletal muscle emphasized elevated energy dissipation and mitochondrial utilisation of fatty acids as fuel substrates in APOE4 mice. Our data suggest that APOE3 has the potential to efficiently harvest dietary energy, accumulate fat in adipose tissue and give higher endurance with lower energy loss in skeletal muscle compared to APOE4. We thus propose that APOE ɛ3 is an energy-thrifty allele compared to ɛ4, which appears to be energy-dissipative. Significance statementThe human Apolipoprotein E (APOE) is a polymorphic gene with three major alleles, ɛ4, ɛ3 and ɛ2, of which ɛ4 is a mortality factor in the elderly and an independent risk factor for age-related diseases.Positive selection of the ɛ3 allele may underlie its worldwide distribution and the high frequency among different populations. However, age-related disease risks associated with ɛ4 are unlikely to have played a significant role in the majority of human evolutionary history. We suggest that APOE ɛ3 carriers have the potential to efficiently harvest dietary energy and accumulate fat in adipose tissue and to express a high level of physical activity especially in times of scarce food supply, rendering ɛ3 an energy-thrifty allele compared to ɛ4.

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Methylenetetrahydrofolate reductase C677T polymorphism is associated with central adiposity and increased androgenicity in healthy postmenopausal women

Cited by 16 publications

References 32 publications

Paraoxonase 1 activity and phenotype distribution in premenopausal and postmenopausal women

Paraoxonase 1 activity and phenotype distribution in premenopausal and postmenopausal women

Methylene Tetrahydrofolate Reductase and Angiotensin Converting Enzyme Gene Polymorphisms Related to Overweight/Obesity among Saudi Subjects from Qassim Region

Apolipoprotein E (APOE) genotype regulates body weight and fatty acid utilization—Studies in gene‐targeted replacement mice

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