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Article ; Online: Role of interleukin 6 signaling pathway in the anti-inflammatory effects of statins on coronary artery disease: Evidence from Mendelian randomization analysis.

Yazdanpanah, Mojgan / Yazdanpanah, Nahid / Chardoli, Mojtaba / Dehghan, Abbas

2024 Volume 406, Page(s) 131964

Abstract: Background: Statins are currently widely used in the prevention of coronary artery disease (CAD) primarily for lipid-lowering with a potential anti-inflammatory effect. However, it is not clear if their potential anti-inflammatory effects are mediated ... ...

Abstract	Background: Statins are currently widely used in the prevention of coronary artery disease (CAD) primarily for lipid-lowering with a potential anti-inflammatory effect. However, it is not clear if their potential anti-inflammatory effects are mediated through the interleukin 6 (IL-6) signaling pathway. Methods: Using the Mendelian randomization (MR) approach followed by multivariable MR analyses, we examined the extent to which the effects of statins on CAD might be mediated through the IL-6 signaling pathway. Results: Our observations showed that HMG-CoA reductase, using LDL levels as a proxy, had a significant effect on upstream IL-6 (βMR = 0.47, P-IVW = 0.01) and nominally significant effects on IL-6RA (βMR = 0.22, P-IVW = 0.047) and APOB (βMR = 0.82, P-IVW = 1.8 × 10-33). While the IL-6 signaling cascade (IL-6RA βMR = -0.06, P-IVW = 3.45 × 10-20 and IL-6 βMR = -0.03, P-IVW = 0.09) and the anti-inflammatory effect of HMG-CoA reductase (βMR = -0.31, P-IVW = 0.01) was found to influence the risk of CAD, the multivariable MR (MVMR) model indicated that the anti-inflammatory effect of HMG-CoA reductase is not likely to be mediated through the IL-6 signaling cascade, including APOB and IL-6RA (MVMRβ = 0.23, P = 0.688). Conclusions: Our findings suggest that statins may use inflammatory mechanisms independent of the IL-6 signaling pathway to prevent CAD. This result could potentially affect the definition of the target population for statin use.
MeSH term(s)	Mendelian Randomization Analysis ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology ; Humans ; Interleukin-6/metabolism ; Interleukin-6/blood ; Coronary Artery Disease/genetics ; Coronary Artery Disease/blood ; Coronary Artery Disease/drug therapy ; Signal Transduction/drug effects ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use ; Polymorphism, Single Nucleotide
Chemical Substances	Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Interleukin-6 ; Anti-Inflammatory Agents ; IL6 protein, human
Language	English
Publishing date	2024-03-19
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	779519-1
ISSN	1874-1754 ; 0167-5273
ISSN (online)	1874-1754
ISSN	0167-5273
DOI	10.1016/j.ijcard.2024.131964
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Zs.A 1673: Show issues

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Article ; Online: Mendelian randomization identifies circulating proteins as biomarkers for age at menarche and age at natural menopause.

Yazdanpanah, Nahid / Jumentier, Basile / Yazdanpanah, Mojgan / Ong, Ken K / Perry, John R B / Manousaki, Despoina

Communications biology

2024 Volume 7, Issue 1, Page(s) 47

Abstract: Age at menarche (AAM) and age at natural menopause (ANM) are highly heritable traits and have been linked to various health outcomes. We aimed to identify circulating proteins associated with altered ANM and AAM using an unbiased two-sample Mendelian ... ...

Abstract	Age at menarche (AAM) and age at natural menopause (ANM) are highly heritable traits and have been linked to various health outcomes. We aimed to identify circulating proteins associated with altered ANM and AAM using an unbiased two-sample Mendelian randomization (MR) and colocalization approach. By testing causal effects of 1,271 proteins on AAM, we identified 22 proteins causally associated with AAM in MR, among which 13 proteins (GCKR, FOXO3, SEMA3G, PATE4, AZGP1, NEGR1, LHB, DLK1, ANXA2, YWHAB, DNAJB12, RMDN1 and HPGDS) colocalized. Among 1,349 proteins tested for causal association with ANM using MR, we identified 19 causal proteins among which 7 proteins (CPNE1, TYMP, DNER, ADAMTS13, LCT, ARL and PLXNA1) colocalized. Follow-up pathway and gene enrichment analyses demonstrated links between AAM-related proteins and obesity and diabetes, and between AAM and ANM-related proteins and various types of cancer. In conclusion, we identified proteomic signatures of reproductive ageing in women, highlighting biological processes at both ends of the reproductive lifespan.
MeSH term(s)	Humans ; Female ; Menarche/genetics ; Mendelian Randomization Analysis ; Proteomics ; Biomarkers ; Menopause/genetics ; HSP40 Heat-Shock Proteins
Chemical Substances	Biomarkers ; DNAJB12 protein, human ; HSP40 Heat-Shock Proteins
Language	English
Publishing date	2024-01-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2399-3642
ISSN (online)	2399-3642
DOI	10.1038/s42003-023-05737-7
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Article: Genetic Variation and Mendelian Randomization Approaches.

Yazdanpanah, Mojgan / Yazdanpanah, Nahid / Manousaki, Despoina

Advances in experimental medicine and biology

2022 Volume 1390, Page(s) 327–342

Abstract: While genome-wide association studies (GWAS) on levels of nuclear receptors are sparse, the genetics of ligands of these receptors (steroid hormones, thyroid hormones, and liposoluble vitamins) have been extensively studied in GWAS of predominantly ... ...

Abstract	While genome-wide association studies (GWAS) on levels of nuclear receptors are sparse, the genetics of ligands of these receptors (steroid hormones, thyroid hormones, and liposoluble vitamins) have been extensively studied in GWAS of predominantly European populations. Hundreds of genetic variants across the genome have been associated with serum levels of nuclear receptor ligands, shedding light on the physiology of hormone metabolism. These GWAS findings have been used to explore causal associations of these hormones with complex human traits and diseases in Mendelian randomization (MR) studies, and in studies using polygenic risk scores to quantify the genetic predisposition to higher/lower hormone levels. As such, besides providing insights into hormonal pathophysiology and its causal relationship with clinical complications, GWAS-identified genetic markers could ultimately play an important role in the daily clinical management of patients. As large trans-ethnic GWAS on levels of nuclear receptor ligands emerge, and with the fast advances in genotyping techniques and constant decrease of the genotyping costs, studying an individual's genetically predicted hormonal profile could be the next step in personalizing the management of patients with pathologies related to nuclear receptors and their ligands.
MeSH term(s)	Genetic Markers ; Genetic Variation ; Genome-Wide Association Study ; Hormones ; Humans ; Ligands ; Mendelian Randomization Analysis ; Vitamins
Chemical Substances	Genetic Markers ; Hormones ; Ligands ; Vitamins
Language	English
Publishing date	2022-09-15
Publishing country	United States
Document type	Journal Article
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-3-031-11836-4_19
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Article ; Online: Connecting Genomics and Proteomics to Identify Protein Biomarkers for Adult and Youth-Onset Type 2 Diabetes: A Two-Sample Mendelian Randomization Study.

Ghanbari, Faegheh / Yazdanpanah, Nahid / Yazdanpanah, Mojgan / Richards, J Brent / Manousaki, Despoina

Diabetes

2022 Volume 71, Issue 6, Page(s) 1324–1337

Abstract: Type 2 diabetes shows an increasing prevalence in both adults and children. Identification of biomarkers for both youth and adult-onset type 2 diabetes is crucial for development of screening tools or drug targets. In this study, using two-sample ... ...

Abstract	Type 2 diabetes shows an increasing prevalence in both adults and children. Identification of biomarkers for both youth and adult-onset type 2 diabetes is crucial for development of screening tools or drug targets. In this study, using two-sample Mendelian randomization (MR), we identified 22 circulating proteins causally linked to adult type 2 diabetes and 11 proteins with suggestive evidence for association with youth-onset type 2 diabetes. Among these, colocalization analysis further supported a role in type 2 diabetes for C-type mannose receptor 2 (MR odds ratio [OR] 0.85 [95% CI 0.79-0.92] per genetically predicted SD increase in protein level), MANS domain containing 4 (MR OR 0.90 [95% CI 0.88-0.92]), sodium/potassium-transporting ATPase subunit β2 (MR OR 1.10 [95% CI 1.06-1.15]), endoplasmic reticulum oxidoreductase 1β (MR OR 1.09 [95% CI 1.05-1.14]), spermatogenesis-associated protein 20 (MR OR 1.12 [95% CI 1.06-1.18]), haptoglobin (MR OR 0.96 [95% CI 0.94-0.98]), and α1-3-N-acetylgalactosaminyltransferase and α1-3-galactosyltransferase (MR OR 1.04 [95% CI 1.03-1.05]). Our findings support a causal role in type 2 diabetes for a set of circulating proteins, which represent promising type 2 diabetes drug targets.
MeSH term(s)	Adolescent ; Adult ; Biomarkers ; Child ; Diabetes Mellitus, Type 2/metabolism ; Genome-Wide Association Study ; Genomics ; Humans ; Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide ; Proteomics
Chemical Substances	Biomarkers
Language	English
Publishing date	2022-03-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	80085-5
ISSN	1939-327X ; 0012-1797
ISSN (online)	1939-327X
ISSN	0012-1797
DOI	10.2337/db21-1046
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Article ; Online: Clinically Relevant Circulating Protein Biomarkers for Type 1 Diabetes: Evidence From a Two-Sample Mendelian Randomization Study.

Yazdanpanah, Nahid / Yazdanpanah, Mojgan / Wang, Ye / Forgetta, Vincenzo / Pollak, Michael / Polychronakos, Constantin / Richards, J Brent / Manousaki, Despoina

Diabetes care

2021 Volume 45, Issue 1, Page(s) 169–177

Abstract: Objective: To identify circulating proteins influencing type 1 diabetes susceptibility using Mendelian randomization (MR).: Research design and methods: We used a large-scale two-sample MR study, using cis genetic determinants (protein quantitative ... ...

Abstract	Objective: To identify circulating proteins influencing type 1 diabetes susceptibility using Mendelian randomization (MR). Research design and methods: We used a large-scale two-sample MR study, using cis genetic determinants (protein quantitative trait loci [pQTL]) of up to 1,611 circulating proteins from five large genome-wide association studies, to screen for causal associations of these proteins with type 1 diabetes risk in 9,684 case subjects with type 1 diabetes and 15,743 control subjects. Further, pleiotropy-robust MR methods were used in sensitivity analyses using both cis and trans-pQTL. Results: We found that a genetically predicted SD increase in signal regulatory protein gamma (SIRPG) level was associated with increased risk of type 1 diabetes risk (MR odds ratio [OR] 1.66 [95% 1.36-2.03]; P = 7.1 × 10-7). The risk of type 1 diabetes increased almost twofold per genetically predicted standard deviation (SD) increase in interleukin-27 Epstein-Barr virus-induced 3 (IL27-EBI3) protein levels (MR OR 1.97 [95% CI 1.48-2.62]; P = 3.7 × 10-6). However, an SD increase in chymotrypsinogen B1 (CTRB1) was associated with decreased risk of type 1 diabetes (MR OR 0.84 [95% CI 0.77-0.90]; P = 6.1 × 10-6). Sensitivity analyses using MR methods testing for pleiotropy while including trans-pQTL showed similar results. While the MR-Egger suggested no pleotropic effect (P value MR-Egger intercept = 0.31), there was evidence of pleiotropy in MR-PRESSO (P value global test = 0.006). Conclusions: We identified three novel circulating protein biomarkers associated with type 1 diabetes risk using an MR approach. These biomarkers are promising targets for development of drugs and/or of screening tools for early prediction of type 1 diabetes.
MeSH term(s)	Biomarkers ; Diabetes Mellitus, Type 1/genetics ; Epstein-Barr Virus Infections ; Genome-Wide Association Study/methods ; Herpesvirus 4, Human ; Humans ; Mendelian Randomization Analysis/methods ; Polymorphism, Single Nucleotide
Chemical Substances	Biomarkers
Language	English
Publishing date	2021-10-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	441231-x
ISSN	1935-5548 ; 0149-5992
ISSN (online)	1935-5548
ISSN	0149-5992
DOI	10.2337/dc21-1049
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Zs.A 1434: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 365: Show issues

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Article: Morquio-like dysostosis multiplex presenting with neuronopathic features is a distinct

Stockler-Ipsiroglu, Sylvia / Yazdanpanah, Nahid / Yazdanpanah, Mojgan / Moisa Popurs, Marioara / Yuskiv, Nataliya / Schmitz Ferreira Santos, Mara Lúcia / Ae Kim, Chong / Fischinger Moura de Souza, Carolina / Marques Lourenço, Charles / Steiner, Carlos Eduardo / Federhen, Andressa / Giugliani, Luciana / Bastos Pereira, Débora Maria / Durán-Carabali, Luz Elena / Giugliani, Roberto

JIMD reports

2021 Volume 60, Issue 1, Page(s) 23–31

Abstract: Background: Morquio B disease (MBD) is a distinct : Objectives and methods: With the aim to further describe patterns of MBD-related dysostosis multiplex, we analyzed clinical, biochemical, and genetic features in 17 cases with : Results: About 14 ...

Abstract	Background: Morquio B disease (MBD) is a distinct Objectives and methods: With the aim to further describe patterns of MBD-related dysostosis multiplex, we analyzed clinical, biochemical, and genetic features in 17 cases with Results: About 14 of the 17 individuals had three or more skeletal findings characteristic of Morquio syndrome. Two had no additional neuronopathic features ( Conclusion: Our study extends the phenotypic spectrum of GLB1-related conditions by describing a cohort of patients with MBD and GM1-gangliosidosis (
Language	English
Publishing date	2021-03-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2672872-2
ISSN	2192-8312 ; 2192-8304
ISSN (online)	2192-8312
ISSN	2192-8304
DOI	10.1002/jmd2.12211
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Article: Maternal Western dietary patterns and the risk of developing a cleft lip with or without a cleft palate.

Vujkovic, Marijana / Ocke, Marga C / van der Spek, Peter J / Yazdanpanah, Nahid / Steegers, Eric A / Steegers-Theunissen, Régine P

Obstetrics and gynecology

2007 Volume 110, Issue 2 Pt 1, Page(s) 378–384

Abstract: Objective: To identify maternal dietary patterns in association with a cleft lip or cleft palate or both in the offspring.: Methods: In a case-control study of 203 mothers of a child with a cleft lip or cleft palate and 178 mothers with non-malformed ...

Abstract	Objective: To identify maternal dietary patterns in association with a cleft lip or cleft palate or both in the offspring. Methods: In a case-control study of 203 mothers of a child with a cleft lip or cleft palate and 178 mothers with non-malformed offspring, maternal nutritional intakes were assessed 14 months after the birth of the index child to estimate the preconception intake. We measured serum and red blood cell folate, serum vitamin B12, whole blood vitamin B6, and total plasma homocysteine as biomarkers. Dietary patterns were analyzed by factor analysis. Univariate and multivariate analyses were performed and odds ratios with 95% confidence intervals calculated. Results: Two major dietary patterns were identified. The Western dietary pattern, eg, high in meat, pizza, legumes, and potatoes, and low in fruits, was associated with a higher risk of a cleft lip or cleft palate (odds ratio 1.9; 95% confidence interval 1.2-3.1). This risk remained significant after adjustment for potential confounders of maternal education and smoking at the time of the study, and periconception use of folic acid or multivitamins. This dietary pattern was associated with lower red blood cell folate (P=.02), vitamin B6 (P=.001), vitamin B12 (P=.02), and higher homocysteine (P=.05) concentrations. The use of the Prudent pattern, eg, high intakes of fish, garlic, nuts, vegetables, increased vitamin B12 (P<.001) and serum folate (P=.05) levels, was not associated with cleft lip or cleft palate risk compared with the Western diet. Conclusion: The use of the maternal Western diet increases the risk of offspring with a cleft lip or cleft palate approximately two fold. Therefore, dietary and lifestyle profiles should be included in preconception screening programs. Level of evidence: II.
MeSH term(s)	Adult ; Case-Control Studies ; Cleft Lip/epidemiology ; Cleft Palate/epidemiology ; Diet ; Female ; Humans ; Infant, Newborn ; Netherlands/epidemiology ; Nutrition Surveys ; Nutritional Status ; Odds Ratio ; Pregnancy ; Risk Factors
Language	English
Publishing date	2007-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	207330-4
ISSN	1873-233X ; 0029-7844
ISSN (online)	1873-233X
ISSN	0029-7844
DOI	10.1097/01.AOG.0000268799.37044.c3
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Article: Low dietary riboflavin but not folate predicts increased fracture risk in postmenopausal women homozygous for the MTHFR 677 T allele.

Yazdanpanah, Nahid / Uitterlinden, André G / Zillikens, M Carola / Jhamai, Mila / Rivadeneira, Fernando / Hofman, Albert / de Jonge, Robert / Lindemans, Jan / Pols, Huibert Ap / van Meurs, Joyce B

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

2008 Volume 23, Issue 1, Page(s) 86–94

Abstract: Unlabelled: The MTHFR C677T polymorphism is associated with mildly elevated homocysteine levels when folate and/or riboflavin status is low. Furthermore, a mildly elevated homocysteine level is a risk factor for osteoporotic fractures. We studied ... ...

Abstract	Unlabelled: The MTHFR C677T polymorphism is associated with mildly elevated homocysteine levels when folate and/or riboflavin status is low. Furthermore, a mildly elevated homocysteine level is a risk factor for osteoporotic fractures. We studied whether dietary intake of riboflavin and folate modifies the effects of the MTHFR C677T variant on fracture risk in 5,035 men and women from the Rotterdam Study. We found that the MTHFR C677T variant interacts with dietary riboflavin intake to influence fracture risk in women. Introduction: The MTHFR C677T polymorphism is associated with mildly elevated homocysteine (Hcy) levels in the presence of low folate and/or riboflavin status. A mildly elevated Hcy level was recently identified as a modifiable risk factor for osteoporotic fracture. We studied whether dietary intake of riboflavin and folate modifies the effects of the MTHFR C677T polymorphism on BMD and fracture risk. Materials and methods: We studied 5,035 individuals from the Rotterdam Study, >or=55 yr of age, who had data available on MTHFR, nutrient intake, and fracture risk. We performed analysis on Hcy levels in a total of 666 individuals, whereas BMD data were present for 4,646 individuals (2,692 women). Results: In the total population, neither the MTHFR C677T polymorphism nor low riboflavin intake was associated with fracture risk and BMD. However, in the lowest quartile of riboflavin intake, female 677-T homozygotes had a 1.8 (95% CI: 1.1-2.9, p = 0.01) times higher risk for incident osteoporotic fractures and a 2.6 (95% CI: 1.3-5.1, p = 0.01) times higher risk for fragility fractures compared with the 677-CC genotype (interaction, p = 0.0002). This effect was not seen for baseline BMD in both men and women. No significant influence was found for dietary folate intake on the association between the MTHFR C677T genotype and fracture risk or BMD. In the lowest quartile of dietary riboflavin intake, T-homozygous individuals (men and women combined) had higher (22.5%) Hcy levels compared with C-homozygotes (mean difference = 3.44 microM, p = 0. 01; trend, p = 0.02). Conclusions: In this cohort of elderly whites, the MTHFR C677T variant interacts with dietary riboflavin intake to influence fracture risk in women.
MeSH term(s)	Aged ; Alleles ; Bone Density ; Cohort Studies ; Female ; Folic Acid/administration & dosage ; Folic Acid Deficiency/complications ; Fractures, Bone/epidemiology ; Fractures, Bone/etiology ; Genotype ; Homocysteine/blood ; Humans ; Incidence ; Male ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics ; Middle Aged ; Osteoporosis, Postmenopausal/complications ; Postmenopause ; Riboflavin/administration & dosage ; Riboflavin Deficiency/complications ; Risk Factors
Chemical Substances	Homocysteine (0LVT1QZ0BA) ; Folic Acid (935E97BOY8) ; Methylenetetrahydrofolate Reductase (NADPH2) (EC 1.5.1.20) ; Riboflavin (TLM2976OFR)
Language	English
Publishing date	2008-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632783-7
ISSN	1523-4681 ; 0884-0431
ISSN (online)	1523-4681
ISSN	0884-0431
DOI	10.1359/jbmr.070812
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Zs.A 2142: Show issues

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Article: The -1997 G/T and Sp1 polymorphisms in the collagen type I alpha1 (COLIA1) gene in relation to changes in femoral neck bone mineral density and the risk of fracture in the elderly: the Rotterdam study.

Yazdanpanah, Nahid / Rivadeneira, Fernando / van Meurs, Joyce B J / Zillikens, M Carola / Arp, P / Hofman, Albert / van Duijn, Cornelia M / Pols, Huibert A P / Uitterlinden, André G

Calcified tissue international

2007 Volume 81, Issue 1, Page(s) 18–25

Abstract: The COLIA1 Sp1 polymorphism has been associated with bone mineral density (BMD) and fracture. A promoter polymorphism, -1997 G/T, also has been associated with BMD. In this study, we examined whether these polymorphisms alone and in the form of ... ...

Abstract	The COLIA1 Sp1 polymorphism has been associated with bone mineral density (BMD) and fracture. A promoter polymorphism, -1997 G/T, also has been associated with BMD. In this study, we examined whether these polymorphisms alone and in the form of haplotypes influence bone parameters and fracture risk in a large population-based cohort of elderly Caucasians. We determined the COLIA1 -1997 G/T (promoter) and Sp1 G/T (intron) polymorphisms in 6,280 individuals and inferred haplotypes. Femoral neck BMD and BMD change were compared across COLIA1 genotypes at baseline and follow-up (mean 6.5 years). We also investigated the relationship between the COLIA1 polymorphisms and incident nonvertebral fractures, which were recorded during a mean follow-up period of 7.4 years. Vertebral fractures were assessed by radiographs on 3,456 genotyped individuals. Femoral neck BMD measured at baseline was 3.8% lower in women carrying two copies of the T-Sp1 allele (P for trend = 0.03). No genotype dependent differences in BMD loss were observed. In women homozygous for the T allele of the Sp1 polymorphism, the risk of fragility fracture increased 2.3 times (95% confidence interval 1.4-3.9, P = 0.001). No such association was observed with the promoter polymorphism. In men, no association with either the Sp1 or the -1997 G/T promoter polymorphism was seen with BMD or fracture. High linkage disequilibrium (LD; D' = 0.99, r (2 )= 0.03) exists between the two studied polymorphisms. We observed three haplotypes in our population: haplotype 1 (G(promoter)-G(intron)) frequency (f) = 69%, haplotype 2 (G(promoter)-T(intron)) f = 17.6%, and haplotype 3 (T(promoter)-G(intron)) f = 13.4%. Haplotype 2 was associated with a 2.1-fold increased risk of fragility fracture in women (95% confidence interval 1.2-3.7, P = 0.001). We confirm that the COLIA1 Sp1 polymorphism influences BMD and the risk of fracture in postmenopausal Caucasian women. In contrast, we found no independent effect of the -1997 G/T promoter polymorphism on BMD or fracture.
MeSH term(s)	Aged ; Bone Density ; Cohort Studies ; Collagen Type I/genetics ; European Continental Ancestry Group ; Female ; Femur Neck/pathology ; Fracture Healing ; Fractures, Bone/genetics ; Humans ; Male ; Middle Aged ; Netherlands ; Polymorphism, Genetic ; Risk
Chemical Substances	Collagen Type I ; collagen type I, alpha 1 chain
Language	English
Publishing date	2007-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	304266-2
ISSN	1432-0827 ; 0171-967X ; 0944-0747 ; 0008-0594
ISSN (online)	1432-0827
ISSN	0171-967X ; 0944-0747 ; 0008-0594
DOI	10.1007/s00223-007-9033-1
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Article: Effect of dietary B vitamins on BMD and risk of fracture in elderly men and women: the Rotterdam study.

Yazdanpanah, Nahid / Zillikens, M Carola / Rivadeneira, Fernando / de Jong, Robert / Lindemans, Jan / Uitterlinden, André G / Pols, Huibert A P / van Meurs, Joyce B J

Bone

2007 Volume 41, Issue 6, Page(s) 987–994

Abstract: A mildly elevated homocysteine (Hcy) level is a novel and potentially modifiable risk factor for age-related osteoporotic fractures. Elevated Hcy levels can have a nutritional cause, such as inadequate intake of folate, riboflavin, pyridoxine or ... ...

Abstract	A mildly elevated homocysteine (Hcy) level is a novel and potentially modifiable risk factor for age-related osteoporotic fractures. Elevated Hcy levels can have a nutritional cause, such as inadequate intake of folate, riboflavin, pyridoxine or cobalamin, which serve as cofactors or substrates for the enzymes involved in the Hcy metabolism. We examined the association between intake of Hcy-related B vitamin (riboflavin, pyridoxine, folate and cobalamin) and femoral neck bone mineral density BMD (FN-BMD) and the risk of fracture in a large population-based cohort of elderly Caucasians. We studied 5304 individuals aged 55 years and over from the Rotterdam Study. Dietary intake of nutrients was obtained from food frequency questionnaires. Incident non-vertebral fractures were recorded during a mean follow-up period of 7.4 years, and vertebral fractures were assessed by X-rays during a mean follow-up period of 6.4 years. We observed a small but significant positive association between dietary pyridoxine (beta = 0.09, p = 1 x 10(-8)) and riboflavin intake (beta = 0.06, p = 0.002) and baseline FN-BMD. In addition, after controlling for gender, age and BMI, pyridoxine intake was inversely correlated to fracture risk. As compared to the three lowest quartiles, individuals in the highest quartile of age- and energy-adjusted dietary pyridoxine intake had a decreased risk of non-vertebral fractures (HR = 0.77, 95% CI = 0.65-0.92, p = 0.005) and of fragility fractures (HR = 0.55, 95% CI = 0.40-0.77, p = 0.0004). Further adjustments for other dietary B vitamins (riboflavin, folate and cobalamin), dietary intake of calcium, vitamin D, vitamin A and vitamin K, protein and energy intake, smoking and BMD did not essentially modify these results. We conclude that increased dietary riboflavin and pyridoxine intake was associated with higher FN-BMD. Furthermore, we found a reduction in risk of fracture in relation to dietary pyridoxine intake independent of BMD. These findings highlight the importance of considering nutritional factors in epidemiological studies of osteoporosis and fractures.
MeSH term(s)	Aged ; Biomarkers ; Bone Density/drug effects ; Diet ; Female ; Fractures, Bone/epidemiology ; Fractures, Bone/prevention & control ; Humans ; Male ; Middle Aged ; Netherlands/epidemiology ; Risk Factors ; Surveys and Questionnaires ; Vitamin B Complex/pharmacology
Chemical Substances	Biomarkers ; Vitamin B Complex (12001-76-2)
Language	English
Publishing date	2007-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632515-4
ISSN	1873-2763 ; 8756-3282
ISSN (online)	1873-2763
ISSN	8756-3282
DOI	10.1016/j.bone.2007.08.021
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