High frequency of vitamin B12 deficiency in asymptomatic individuals homozygous to MTHFR C677T mutation is associated with endothelial dysfunction and homocysteinemia
Departments of 1 Cardiovascular Medicine and 2 Molecular Hematology, Lady Davis Carmel Medical Center, and the 3 Ruth and Bruce Rappaport Faculty of Medicine, Technion IIT, Haifa, Israel Submitted 30 October 2006 ; accepted in final form 11 April 2007 The aim of this study was to examine the associa...
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| container_title | American journal of physiology. Heart and circulatory physiology |
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| creator | Zittan, E Preis, M Asmir, I Cassel, A Lindenfeld, N Alroy, S Halon, D. A Lewis, B. S Shiran, A Schliamser, J. E Flugelman, M. Y |
| description | Departments of 1 Cardiovascular Medicine and 2 Molecular Hematology, Lady Davis Carmel Medical Center, and the 3 Ruth and Bruce Rappaport Faculty of Medicine, Technion IIT, Haifa, Israel
Submitted 30 October 2006
; accepted in final form 11 April 2007
The aim of this study was to examine the association of homozygosity for the methylenetetrahydrofolate reductase (MTHFR) C677T mutation and vitamin B12 deficiency in 360 asymptomatic individuals and to investigate forearm endothelial function in C677T homozygotes. MTHFR C677T mutation and levels of vitamin B12, folic acid, and homocysteine were measured in study participants. Frequency of homozygosity for the C677T mutation was 67/360 (18.6%). Homocysteine levels were elevated in homozygous compared with heterozygous subjects or those without the mutation (20.6 ± 18.8 vs. 9.4 ± 3.2 µmol/l; P < 0.0001). The number of subjects with vitamin B12 deficiency ( |
| doi_str_mv | 10.1152/ajpheart.01189.2006 |
| format | Article |
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Submitted 30 October 2006
; accepted in final form 11 April 2007
The aim of this study was to examine the association of homozygosity for the methylenetetrahydrofolate reductase (MTHFR) C677T mutation and vitamin B12 deficiency in 360 asymptomatic individuals and to investigate forearm endothelial function in C677T homozygotes. MTHFR C677T mutation and levels of vitamin B12, folic acid, and homocysteine were measured in study participants. Frequency of homozygosity for the C677T mutation was 67/360 (18.6%). Homocysteine levels were elevated in homozygous compared with heterozygous subjects or those without the mutation (20.6 ± 18.8 vs. 9.4 ± 3.2 µmol/l; P < 0.0001). The number of subjects with vitamin B12 deficiency (<150 pmol/l) was significantly higher among the homozygote than the heterozygote subjects or subjects without mutation [20/67 (29.8%) vs. 27/293 (9.2%); P < 0.0001]. Homozygote subjects had 4.2 times higher probability of having B12 deficiency (95% confidence interval = 2.18.3). Forearm endothelial function was assessed in 33 homozygote and 12 control subjects. Abnormal endothelial function was observed in homozygous subjects and was worse in homozygote subjects with vitamin B12 deficiency. Endothelial function was normalized after B12 and folic acid treatment. We found that homozygosity for the C677T mutation is strongly associated with B12 deficiency. Coexistence of homozygosity for the C677T mutation and B12 deficiency is associated with endothelial dysfunction and can be corrected with vitamin B12 and folic acid treatment.
homocysteine; endothelial function
Address for reprint requests and other correspondence: M. Y. Flugelman, Dept. of Cardiovascular Medicine, Lady Davis Carmel Medical Center, 7 Michal St., Haifa, Israel 34632 (e-mail: myf{at}tx.technion.ac.il )</description><identifier>ISSN: 0363-6135</identifier><identifier>EISSN: 1522-1539</identifier><identifier>DOI: 10.1152/ajpheart.01189.2006</identifier><identifier>PMID: 17449548</identifier><identifier>CODEN: AJPPDI</identifier><language>eng</language><publisher>United States: American Physiological Society</publisher><subject>Adult ; Cohort Studies ; Comorbidity ; Female ; Genetic Predisposition to Disease - epidemiology ; Genetic Predisposition to Disease - genetics ; Genetic Testing - methods ; Humans ; Hyperhomocysteinemia - epidemiology ; Hyperhomocysteinemia - genetics ; Incidence ; Israel - epidemiology ; Male ; Medical treatment ; Methylenetetrahydrofolate Reductase (NADPH2) - genetics ; Mutation ; Risk Assessment - methods ; Risk Factors ; Studies ; Vascular Diseases - epidemiology ; Vascular Diseases - genetics ; Vitamin B ; Vitamin B 12 Deficiency - epidemiology ; Vitamin B 12 Deficiency - genetics</subject><ispartof>American journal of physiology. Heart and circulatory physiology, 2007-07, Vol.293 (1), p.H860-H865</ispartof><rights>Copyright American Physiological Society Jul 2007</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c420t-9310a8e676fe0ce8e54c3b00af5f612395734db14e8c23f05aa5321d5a6c5a733</citedby><cites>FETCH-LOGICAL-c420t-9310a8e676fe0ce8e54c3b00af5f612395734db14e8c23f05aa5321d5a6c5a733</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,3039,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17449548$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zittan, E</creatorcontrib><creatorcontrib>Preis, M</creatorcontrib><creatorcontrib>Asmir, I</creatorcontrib><creatorcontrib>Cassel, A</creatorcontrib><creatorcontrib>Lindenfeld, N</creatorcontrib><creatorcontrib>Alroy, S</creatorcontrib><creatorcontrib>Halon, D. A</creatorcontrib><creatorcontrib>Lewis, B. S</creatorcontrib><creatorcontrib>Shiran, A</creatorcontrib><creatorcontrib>Schliamser, J. E</creatorcontrib><creatorcontrib>Flugelman, M. Y</creatorcontrib><title>High frequency of vitamin B12 deficiency in asymptomatic individuals homozygous to MTHFR C677T mutation is associated with endothelial dysfunction and homocysteinemia</title><title>American journal of physiology. Heart and circulatory physiology</title><addtitle>Am J Physiol Heart Circ Physiol</addtitle><description>Departments of 1 Cardiovascular Medicine and 2 Molecular Hematology, Lady Davis Carmel Medical Center, and the 3 Ruth and Bruce Rappaport Faculty of Medicine, Technion IIT, Haifa, Israel
Submitted 30 October 2006
; accepted in final form 11 April 2007
The aim of this study was to examine the association of homozygosity for the methylenetetrahydrofolate reductase (MTHFR) C677T mutation and vitamin B12 deficiency in 360 asymptomatic individuals and to investigate forearm endothelial function in C677T homozygotes. MTHFR C677T mutation and levels of vitamin B12, folic acid, and homocysteine were measured in study participants. Frequency of homozygosity for the C677T mutation was 67/360 (18.6%). Homocysteine levels were elevated in homozygous compared with heterozygous subjects or those without the mutation (20.6 ± 18.8 vs. 9.4 ± 3.2 µmol/l; P < 0.0001). The number of subjects with vitamin B12 deficiency (<150 pmol/l) was significantly higher among the homozygote than the heterozygote subjects or subjects without mutation [20/67 (29.8%) vs. 27/293 (9.2%); P < 0.0001]. Homozygote subjects had 4.2 times higher probability of having B12 deficiency (95% confidence interval = 2.18.3). Forearm endothelial function was assessed in 33 homozygote and 12 control subjects. Abnormal endothelial function was observed in homozygous subjects and was worse in homozygote subjects with vitamin B12 deficiency. Endothelial function was normalized after B12 and folic acid treatment. We found that homozygosity for the C677T mutation is strongly associated with B12 deficiency. Coexistence of homozygosity for the C677T mutation and B12 deficiency is associated with endothelial dysfunction and can be corrected with vitamin B12 and folic acid treatment.
homocysteine; endothelial function
Address for reprint requests and other correspondence: M. Y. Flugelman, Dept. of Cardiovascular Medicine, Lady Davis Carmel Medical Center, 7 Michal St., Haifa, Israel 34632 (e-mail: myf{at}tx.technion.ac.il )</description><subject>Adult</subject><subject>Cohort Studies</subject><subject>Comorbidity</subject><subject>Female</subject><subject>Genetic Predisposition to Disease - epidemiology</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Genetic Testing - methods</subject><subject>Humans</subject><subject>Hyperhomocysteinemia - epidemiology</subject><subject>Hyperhomocysteinemia - genetics</subject><subject>Incidence</subject><subject>Israel - epidemiology</subject><subject>Male</subject><subject>Medical treatment</subject><subject>Methylenetetrahydrofolate Reductase (NADPH2) - genetics</subject><subject>Mutation</subject><subject>Risk Assessment - methods</subject><subject>Risk Factors</subject><subject>Studies</subject><subject>Vascular Diseases - epidemiology</subject><subject>Vascular Diseases - genetics</subject><subject>Vitamin B</subject><subject>Vitamin B 12 Deficiency - epidemiology</subject><subject>Vitamin B 12 Deficiency - genetics</subject><issn>0363-6135</issn><issn>1522-1539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kcuO0zAYRiMEYsrAEyAhiwW7FF9iJ2HHVJQiDUJCZW259u_GVRKH2JkhPBDPiactVEJiZdk-5_Ply7KXBC8J4fStOgwNqDEuMSFVvaQYi0fZIu3QnHBWP84WmAmWC8L4VfYshAPGmJeCPc2uSFkUNS-qRfZr4_YNsiN8n6DXM_IW3bmoOtejG0KRAeu0O-6kFRXmboi-U9HpNDfuzplJtQE1vvM_572fAooefd5u1l_RSpTlFnVTTLTvkQtJD147FcGgexcbBL3xsYHWqRaZOdip10dU9eaYqOcQwfXQOfU8e2LTQfDiPF5n39YftqtNfvvl46fV-9tcFxTHvGYEqwpEKSxgDRXwQrMdxspyKwhlNS9ZYXakgEpTZjFXijNKDFdCc1Uydp29OeUOo08_EqLsXNDQtqqH9DpZ4hLXRNAEvv4HPPhp7NPdJKW14JUoeYLYCdKjD2EEK4fRdWqcJcHyoUP5p0N57FA-dJisV-foadeBuTjn0hKwPAFN6u7ejSCHZg7Ot34_XxJpzSSRm0rgJLz7v7Ce2nYLP-Jf8yLKwVj2G0xxws0</recordid><startdate>20070701</startdate><enddate>20070701</enddate><creator>Zittan, E</creator><creator>Preis, M</creator><creator>Asmir, I</creator><creator>Cassel, A</creator><creator>Lindenfeld, N</creator><creator>Alroy, S</creator><creator>Halon, D. A</creator><creator>Lewis, B. S</creator><creator>Shiran, A</creator><creator>Schliamser, J. E</creator><creator>Flugelman, M. Y</creator><general>American Physiological Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TS</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20070701</creationdate><title>High frequency of vitamin B12 deficiency in asymptomatic individuals homozygous to MTHFR C677T mutation is associated with endothelial dysfunction and homocysteinemia</title><author>Zittan, E ; Preis, M ; Asmir, I ; Cassel, A ; Lindenfeld, N ; Alroy, S ; Halon, D. A ; Lewis, B. S ; Shiran, A ; Schliamser, J. E ; Flugelman, M. 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A</creatorcontrib><creatorcontrib>Lewis, B. S</creatorcontrib><creatorcontrib>Shiran, A</creatorcontrib><creatorcontrib>Schliamser, J. E</creatorcontrib><creatorcontrib>Flugelman, M. Y</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Physical Education Index</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of physiology. Heart and circulatory physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zittan, E</au><au>Preis, M</au><au>Asmir, I</au><au>Cassel, A</au><au>Lindenfeld, N</au><au>Alroy, S</au><au>Halon, D. A</au><au>Lewis, B. S</au><au>Shiran, A</au><au>Schliamser, J. E</au><au>Flugelman, M. Y</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High frequency of vitamin B12 deficiency in asymptomatic individuals homozygous to MTHFR C677T mutation is associated with endothelial dysfunction and homocysteinemia</atitle><jtitle>American journal of physiology. Heart and circulatory physiology</jtitle><addtitle>Am J Physiol Heart Circ Physiol</addtitle><date>2007-07-01</date><risdate>2007</risdate><volume>293</volume><issue>1</issue><spage>H860</spage><epage>H865</epage><pages>H860-H865</pages><issn>0363-6135</issn><eissn>1522-1539</eissn><coden>AJPPDI</coden><abstract>Departments of 1 Cardiovascular Medicine and 2 Molecular Hematology, Lady Davis Carmel Medical Center, and the 3 Ruth and Bruce Rappaport Faculty of Medicine, Technion IIT, Haifa, Israel
Submitted 30 October 2006
; accepted in final form 11 April 2007
The aim of this study was to examine the association of homozygosity for the methylenetetrahydrofolate reductase (MTHFR) C677T mutation and vitamin B12 deficiency in 360 asymptomatic individuals and to investigate forearm endothelial function in C677T homozygotes. MTHFR C677T mutation and levels of vitamin B12, folic acid, and homocysteine were measured in study participants. Frequency of homozygosity for the C677T mutation was 67/360 (18.6%). Homocysteine levels were elevated in homozygous compared with heterozygous subjects or those without the mutation (20.6 ± 18.8 vs. 9.4 ± 3.2 µmol/l; P < 0.0001). The number of subjects with vitamin B12 deficiency (<150 pmol/l) was significantly higher among the homozygote than the heterozygote subjects or subjects without mutation [20/67 (29.8%) vs. 27/293 (9.2%); P < 0.0001]. Homozygote subjects had 4.2 times higher probability of having B12 deficiency (95% confidence interval = 2.18.3). Forearm endothelial function was assessed in 33 homozygote and 12 control subjects. Abnormal endothelial function was observed in homozygous subjects and was worse in homozygote subjects with vitamin B12 deficiency. Endothelial function was normalized after B12 and folic acid treatment. We found that homozygosity for the C677T mutation is strongly associated with B12 deficiency. Coexistence of homozygosity for the C677T mutation and B12 deficiency is associated with endothelial dysfunction and can be corrected with vitamin B12 and folic acid treatment.
homocysteine; endothelial function
Address for reprint requests and other correspondence: M. Y. Flugelman, Dept. of Cardiovascular Medicine, Lady Davis Carmel Medical Center, 7 Michal St., Haifa, Israel 34632 (e-mail: myf{at}tx.technion.ac.il )</abstract><cop>United States</cop><pub>American Physiological Society</pub><pmid>17449548</pmid><doi>10.1152/ajpheart.01189.2006</doi></addata></record> |
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| subjects | Adult Cohort Studies Comorbidity Female Genetic Predisposition to Disease - epidemiology Genetic Predisposition to Disease - genetics Genetic Testing - methods Humans Hyperhomocysteinemia - epidemiology Hyperhomocysteinemia - genetics Incidence Israel - epidemiology Male Medical treatment Methylenetetrahydrofolate Reductase (NADPH2) - genetics Mutation Risk Assessment - methods Risk Factors Studies Vascular Diseases - epidemiology Vascular Diseases - genetics Vitamin B Vitamin B 12 Deficiency - epidemiology Vitamin B 12 Deficiency - genetics |
| title | High frequency of vitamin B12 deficiency in asymptomatic individuals homozygous to MTHFR C677T mutation is associated with endothelial dysfunction and homocysteinemia |
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