The synergistic effect of bone mineral density and methylenetetrahydrofolate reductase (MTHFR) polymorphism (C677T) on fractures

Mapping Intimacies ◽

10.31234/osf.io/taq7f ◽

2020 ◽

Author(s):

Lungwani Muungo

Keyword(s):

Risk Factor ◽

Methylenetetrahydrofolate Reductase ◽

Body Height ◽

Hazard Ratio ◽

Mineral Density ◽

Mthfr Polymorphism ◽

Allele Variant ◽

Future Fracture ◽

Turnover Markers ◽

Traditional Risk Factors

A functional polymorphism in methylenetetrahydrofolatereductase (MTHFR) has been identifi ed at codon677 (C677T). The T-allele variant (valine type) has lowerenzyme activity than the wild type (C-allele or alaninetype), resulting in a slightly elevated homocysteine level,which has been recently recognized as a risk factor for fracture.However, whether subjects bearing the T allele havehigher susceptibility to fractures is still controversial. Wehave investigated the effects of MTHFR polymorphism onfracture susceptibility in Japanese postmenopausal women.A total of 502 postmenopausal ambulatory Japanese womenwere followed up for 5.1 ± 3.4 (mean ± SD) years, and atotal of 155 patients with incident fractures (121 patientswith vertebral fractures and 34 cases with fractures at othersites) were recorded. When compared with the patientswithout any fractures, the patients with incident fractureswere older, had more prevalent fractures, had higher urinarylevels of bone turnover markers as well as plasma homocysteinelevel, but were shorter in body height and had lowerbone mineral density. The prevalence of the TT genotypeof MTHFR was signifi cantly higher in the patients withincident fractures compared to the other genotypes. Thesubjects with the TT genotype had a higher incidence rateof fracture and higher plasma level of homocysteine thanthe subjects bearing the non-TT genotype. This relationshipwas observed in both osteoporotic and nonosteoporoticgroups. The hazard ratio for TT genotype without osteoporosis,non-TT genotype with osteoporosis, and TT genotypewith osteoporosis was 1.49 (0.91–2.45), 3.64 (2.50–5.29),and 7.21 (4.34–11.97), respectively, compared to the non-TTgenotype without osteoporosis. A higher hazard ratio forthe TT genotype with osteoporosis was still apparent afteradjustment for age, body size, and number of prevalentvertebral fractures. These results indicate that the TT genotypeof MTHFR may be a risk factor for future fracture inaddition to the traditional risk factors.

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Is MTHFR polymorphism a risk factor for Alzheimer's disease like APOE?

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2005000100001 ◽

2005 ◽

Vol 63 (1) ◽

pp. 1-6 ◽

Cited By ~ 22

Author(s):

Liana Lisboa Fernandez ◽

Rosane Machado Scheibe

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Risk Factor ◽

Methylenetetrahydrofolate Reductase ◽

Venous Blood ◽

Dna Amplification ◽

Mthfr Gene ◽

Chi Square ◽

Mthfr Polymorphism ◽

Significant Difference

BACKGROUND: The role of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms as risk factors for the occurence of Alzheimer's disease (AD) is still controversial: OBJECTIVE: To verify the association between MTHFR and apolipoprotein E (APOE) polymorphisms and Alzheimer's disease. METHOD: This work was conducted as a case-control study. Cases included thirty patients with probable AD. Controls were constituted by 29 individuals without dementia according to neuropsychological tests paired to age, sex, race and educational level. DNA was isolated from peripheral leukocytes of anticoagulated venous blood. Genotyping of APOE and MTHFR were performed by DNA amplification and digestion. The frequences of APOE and MTHFR genotypes were submitted by chi-square test corrected by Fisher test; the APOE genotypes, to chi-square linear tendency test and the frequences of MTHFR mutant and AD, by stratificated anlysis adjust by Mantel-Haenszel method. RESULTS: There was significant difference about APOE4 and APOE2 in the groups. (p=0.002) The odds ratio increased exponentially with the increased number of E4 allele (chi2 linear tendency test). No significant difference was detected on MTHFR genotypes in both case and control groups. CONCLUSION: The APOE4 is a risk factor and demonstrated a dose-depenent effect while APOE2 allele conferred a protection to AD. The MTHFR mutation had no correlation with AD.

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The synergistic effect of bone mineral density and methylenetetrahydrofolate reductase (MTHFR) polymorphism (C677T) on fractures

Journal of Bone and Mineral Metabolism ◽

10.1007/s00774-008-0878-9 ◽

2008 ◽

Vol 26 (6) ◽

pp. 595-602 ◽

Cited By ~ 35

Author(s):

Masataka Shiraki ◽

Tomohiko Urano ◽

Tatsuhiko Kuroda ◽

Mitsuru Saito ◽

Shiro Tanaka ◽

...

Keyword(s):

Bone Mineral Density ◽

Synergistic Effect ◽

Bone Mineral ◽

Methylenetetrahydrofolate Reductase ◽

Mineral Density ◽

Mthfr Polymorphism

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Association of Methylenetetrahydrofolate Reductase (MTHFR) Polymorphism with Bone Mineral Density in Postmenopausal Japanese Women

Calcified Tissue International ◽

10.1007/s002230010038 ◽

2000 ◽

Vol 66 (3) ◽

pp. 190-194 ◽

Cited By ~ 90

Author(s):

M. Miyao ◽

H. Morita ◽

T. Hosoi ◽

H. Kurihara ◽

S. Inoue ◽

...

Keyword(s):

Bone Mineral Density ◽

Bone Mineral ◽

Methylenetetrahydrofolate Reductase ◽

Japanese Women ◽

Mineral Density ◽

Mthfr Polymorphism

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Polymorphisms of Methylenetetrahydrofolate Reductase Gene and Risk of Ischemic Stroke in a Spanish Population.

Blood ◽

10.1182/blood.v104.11.3515.3515 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3515-3515

Author(s):

Raquel De Ona ◽

Pilar Llamas ◽

Jaime Fernandez De Velasco ◽

Ana Belen Santos ◽

Elena Meseguer ◽

...

Keyword(s):

Regression Analysis ◽

Risk Factor ◽

Methylenetetrahydrofolate Reductase ◽

Mthfr Gene ◽

Wild Type ◽

Mthfr Polymorphism ◽

Reductase Gene ◽

677T Allele ◽

Methylenetetrahydrofolate Reductase Gene ◽

1298C Allele

Abstract Ischemic stroke (IS) is a multifactorial disease caused by the interaction of genetic and environmental factors. The question of whether mild hyperhomocysteiemia (Hcy) is a risk factor for CVD has been debated and is still unclear. Common single nucleotide polymorphisms (C677T and A1298C) in the methylenetetrahydrofolate reductase gene (MTHFR) decrease the activity of the enzyme, leading to hyperhomocysteinemia, particularly in folate-deficient states. We investigated whether there is a link between MTHFR gene C677T and A1298C polymorphisms or plasma homocysteine and IS. Patients and methods: Genotypic analyses were performed on 308 consecutive unrelated patients diagnosed with IS, 147 women and 161 men, mean age 700.8 years, who were diagnosed according to the Trial of Org 10172 in Acute Stroke Treatment. All included cases were age and sex matched to a control from the same geographic area who had no history of vascular disease. Patients and controls completed a questionnaires including blood pressure, diabetes status, total serum cholesterol level and smoking history. Genetic tests were performed by RFLP-PCR and homocysteine levels in plasma were measured by ELISA method. The strength of the association of the polymorphisms with the occurrence of IS was estimated by calculation of the OR and its 95%CI by exact method. P values less than 0.05 were considered significant. Logistic regression analysis was applied to estimate the risk in a multivariable predictive model with dependent variable (case/control) and all independent variables significant in the bivariate analysis. SPSS 9.0 was used for the statistical analysis. Results: The distribution of MTHFR gene C677T genotypes in patients (or controls) was: CC-genotype in 134 cases, 44.1% (155 controls, 50.5%); CT-genotype in 131 cases, 43.1% (138 controls, 44.9%); and TT-genotype in 39 cases, 12.8% (14 controls, 4.6%). The distribution of MTHFR gene A1298C genotypes in patients (or controls) was: AA-genotype in 164 cases, 55.6% (127 controls, 41.2%); AC-genotype in 113 cases, 38.3% (149 controls, 48.4%); and CC-genotype in 18 cases, 6.1% (32 controls, 10.4%). Genotype analysis showed a significant higher prevalence of the TT-genotype of MTHFR C677T in patients (p= 0.001;OR= 3.08;95%CI= 1.63–5.79). Nevertheless, genotype analysis showed a lower prevalence of the CC genotype of MTHFR A1298C in patients (p= 0.056;OR= 0.56;95%CI= 0.3–1.02). The genetic analysis was similar for the different subtypes of IS. Homocysteine plasma level was significantly higher in homozygosity for 677T allele than wild type (20.2±9.3 mmol/l and 17.4±6.5 mmol/l; p=0.029) and was lower in homozygosity for 1298C allele than wild type (16.2±5.7 mmol/l and 18.7±9.0 mmol/l; p=0.029). Homocysteine plasma levels in doubly heterozygous for C677T and A1298C mutations in the MTHFR gene were higher than the other genotypes (20.6±8.4 mmol/l and 18.6±8.3 mmol/l; p= 0.133). Logistic regression analysis showed a independent association of 677T allele of MTHFRwith CVD. Also hypertension, diabetes mellitus and current smoking status were statistically associated with CVD. Conclusions: Our findings suggest that the T allele of 677 MTHFR polymorphism is a genetic risk factor for IS in Spanish population. The unexpected protective effect of the 1298C allele of 1298 MTHFR polymorphism for IS needs further study. Supported by Grant FIS 03/0176. Oa R: Fundacion Conchita Rabago Grant. Santos AB: Fundacion LAIR 2004 Grant.

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PTHR1 Genetic Polymorphisms Are Associated with Osteoporosis among Postmenopausal Arab Women

BioMed Research International ◽

10.1155/2021/2993761 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Saba Abdi ◽

Abeer Abdulaziz Almiman ◽

Mohammed Ghouse Ahmed Ansari ◽

Abdullah M. Alnaami ◽

Abdul Khader Mohammed ◽

...

Keyword(s):

Risk Factor ◽

Parathyroid Hormone ◽

Inflammatory Markers ◽

Significant Risk ◽

Significant Risk Factor ◽

Control Group ◽

Arab Women ◽

Mineral Density ◽

25 Hydroxy Vitamin D ◽

Turnover Markers

The parathyroid hormone 1 receptor (PTHR1) plays a crucial role in calcium homeostasis and bone metabolism. However, its genetic role in regulating bone turnover markers (BTMs) in postmenopausal osteoporosis (PMO) remains unclear. Herein, we explored parathyroid hormone (PTH) and PTHR gene variant susceptibility to osteoporosis and their association with various circulating BTM and inflammatory markers in postmenopausal women of Arab ethnicity. In total, 600 postmenopausal Arab women (300-PMO and 300-control) were genotyped for selected SNPs in PTH (rs1459015, rs307253, rs6054, rs307247, rs10500783 and rs10500784), PTHR1 (rs6442037, rs1138518, and rs724449 SNPs) and PTHR2 (rs9288393, rs10497900, and rs897083). Anthropometrics, BTMs, and inflammatory markers were measured. Bone mineral density (BMD) was measured at the lumbar spine L1–L4 and the femoral neck using dual-energy X-ray absorptiometry (DXA). PTHR1 rs1138518 genotype C/T was found to be a significant risk factor for PMO ( OR = 1.49 , 95% CI 1.0-2.1, P = 0.03 ). The genotypes C/T and T/T of PTHR1 rs1138518 were associated with 25-hydroxy-vitamin D (25(OH)D) regulation. In the PMO group, carriers of the C/T genotype had significantly lower 25(OH)D levels than carriers of the same genotypes in the control group (59.9 (36.7-92.4) nmol/l and 66.4 (43.5-87.8) nmol/l, respectively; P = 0.048 ]. Our study concludes that the PTHR1 rs1138518 genotype could be a potential risk factor for osteoporosis and 25(OH)D regulation in Arab women with PMO.

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B-Vitamins, Methylenetetrahydrofolate Reductase (MTHFR) and Hypertension

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000069 ◽

2011 ◽

Vol 81 (4) ◽

pp. 240-244 ◽

Cited By ~ 14

Author(s):

Mary Ward ◽

Carol P Wilson ◽

J J Strain ◽

Geraldine Horigan ◽

John M. Scott ◽

...

Keyword(s):

Blood Pressure ◽

Cardiovascular Disease ◽

Risk Factor ◽

Low Dose ◽

Methylenetetrahydrofolate Reductase ◽

Genetic Determinant ◽

Gene Encoding ◽

Homocysteine Concentration ◽

Homozygous Mutant ◽

B Vitamin

Hypertension is a leading risk factor for cardiovascular disease (CVD) and stroke. A common polymorphism in the gene encoding the enzyme methylenetetrahydrofolate reductase (MTHFR), previously identified as the main genetic determinant of elevated homocysteine concentration and also recognized as a risk factor for CVD, appears to be independently associated with hypertension. The B-vitamin riboflavin is required as a cofactor by MTHFR and recent evidence suggests it may have a role in modulating blood pressure, specifically in those with the homozygous mutant MTHFR 677 TT genotype. If studies confirm that this genetic predisposition to hypertension is correctable by low-dose riboflavin, the findings could have important implications for the management of hypertension given that the frequency of this polymorphism ranges from 3 to 32 % worldwide.

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