Homocysteine Metabolism Gene Polymorphisms (MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) Jointly Elevate the Risk of Folate Deficiency
Folate deficiency is strongly associated with cardiovascular disease. We aimed to explore the joint effect of the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, methionine synthase (MTR) A2756G, and methionine synthase reductase (MTRR) A66G polymorphisms on folate deficiency in a Chin...
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| Veröffentlicht in: | Nutrients 2015-08, Vol.7 (8), p.6670-6687 |
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| creator | Li, Wen-Xing Dai, Shao-Xing Zheng, Jun-Juan Liu, Jia-Qian Huang, Jing-Fei |
| description | Folate deficiency is strongly associated with cardiovascular disease. We aimed to explore the joint effect of the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, methionine synthase (MTR) A2756G, and methionine synthase reductase (MTRR) A66G polymorphisms on folate deficiency in a Chinese hypertensive population. A total of 480 subjects aged 28-75 were enrolled in this study from September 2005-December 2005 from six hospitals in different Chinese regions. Known genotypes were detected by PCR-RFLP methods and serum folate was measured by chemiluminescence immunoassay. Our results showed that MTHFR 677TT and MTR 2756AG + GG were independently associated with a higher risk of folate deficiency (TT vs. CC + CT, p < 0.001 and AG + GG vs. AA p = 0.030, respectively). However, the MTHFR A1298C mutation may confer protection by elevating the serum folate level (p = 0.025). Furthermore, patients carrying two or more risk genotypes showed higher odds of folate deficiency than null risk genotype carriers, especially those carrying four risk genotypes. These findings were verified by generalized multifactor dimensionality reduction (p = 0.0107) and a cumulative effects model (p = 0.001). The results of this study have shown that interactions among homocysteine metabolism gene polymorphisms lead to dramatic elevations in the folate deficiency risk. |
| doi_str_mv | 10.3390/nu7085303 |
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We aimed to explore the joint effect of the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, methionine synthase (MTR) A2756G, and methionine synthase reductase (MTRR) A66G polymorphisms on folate deficiency in a Chinese hypertensive population. A total of 480 subjects aged 28-75 were enrolled in this study from September 2005-December 2005 from six hospitals in different Chinese regions. Known genotypes were detected by PCR-RFLP methods and serum folate was measured by chemiluminescence immunoassay. Our results showed that MTHFR 677TT and MTR 2756AG + GG were independently associated with a higher risk of folate deficiency (TT vs. CC + CT, p < 0.001 and AG + GG vs. AA p = 0.030, respectively). However, the MTHFR A1298C mutation may confer protection by elevating the serum folate level (p = 0.025). Furthermore, patients carrying two or more risk genotypes showed higher odds of folate deficiency than null risk genotype carriers, especially those carrying four risk genotypes. These findings were verified by generalized multifactor dimensionality reduction (p = 0.0107) and a cumulative effects model (p = 0.001). The results of this study have shown that interactions among homocysteine metabolism gene polymorphisms lead to dramatic elevations in the folate deficiency risk.</description><identifier>ISSN: 2072-6643</identifier><identifier>EISSN: 2072-6643</identifier><identifier>DOI: 10.3390/nu7085303</identifier><identifier>PMID: 26266420</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase - genetics ; Adult ; Aged ; Asian Continental Ancestry Group - genetics ; Blood Pressure ; blood serum ; Body Mass Index ; cardiovascular diseases ; chemiluminescence immunoassays ; Dihydrofolate reductase ; Double-Blind Method ; Female ; Ferredoxin-NADP Reductase - genetics ; folic acid ; Folic Acid - blood ; Folic Acid Deficiency - blood ; Folic Acid Deficiency - genetics ; genotype ; Genotyping Techniques ; Homocysteine ; Homocysteine - metabolism ; hospitals ; Humans ; Hypertension ; Incidence ; Laboratories ; Linear Models ; Male ; Metabolism ; methionine synthase ; methylenetetrahydrofolate reductase ; Methylenetetrahydrofolate Reductase (NADPH2) - genetics ; Middle Aged ; Mutation ; patients ; Polymerase Chain Reaction ; Polymorphism ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; restriction fragment length polymorphism ; Vitamin B ; vitamin B deficiency</subject><ispartof>Nutrients, 2015-08, Vol.7 (8), p.6670-6687</ispartof><rights>Copyright MDPI AG 2015</rights><rights>2015 by the authors; licensee MDPI, Basel, Switzerland. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c535t-9f727259827c25091c5b91671fa46e583d3ffc651d38579b3f7d5a995e556efe3</citedby><cites>FETCH-LOGICAL-c535t-9f727259827c25091c5b91671fa46e583d3ffc651d38579b3f7d5a995e556efe3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4555142/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4555142/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26266420$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Wen-Xing</creatorcontrib><creatorcontrib>Dai, Shao-Xing</creatorcontrib><creatorcontrib>Zheng, Jun-Juan</creatorcontrib><creatorcontrib>Liu, Jia-Qian</creatorcontrib><creatorcontrib>Huang, Jing-Fei</creatorcontrib><title>Homocysteine Metabolism Gene Polymorphisms (MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) Jointly Elevate the Risk of Folate Deficiency</title><title>Nutrients</title><addtitle>Nutrients</addtitle><description>Folate deficiency is strongly associated with cardiovascular disease. We aimed to explore the joint effect of the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, methionine synthase (MTR) A2756G, and methionine synthase reductase (MTRR) A66G polymorphisms on folate deficiency in a Chinese hypertensive population. A total of 480 subjects aged 28-75 were enrolled in this study from September 2005-December 2005 from six hospitals in different Chinese regions. Known genotypes were detected by PCR-RFLP methods and serum folate was measured by chemiluminescence immunoassay. Our results showed that MTHFR 677TT and MTR 2756AG + GG were independently associated with a higher risk of folate deficiency (TT vs. CC + CT, p < 0.001 and AG + GG vs. AA p = 0.030, respectively). However, the MTHFR A1298C mutation may confer protection by elevating the serum folate level (p = 0.025). Furthermore, patients carrying two or more risk genotypes showed higher odds of folate deficiency than null risk genotype carriers, especially those carrying four risk genotypes. These findings were verified by generalized multifactor dimensionality reduction (p = 0.0107) and a cumulative effects model (p = 0.001). The results of this study have shown that interactions among homocysteine metabolism gene polymorphisms lead to dramatic elevations in the folate deficiency risk.</description><subject>5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase - genetics</subject><subject>Adult</subject><subject>Aged</subject><subject>Asian Continental Ancestry Group - genetics</subject><subject>Blood Pressure</subject><subject>blood serum</subject><subject>Body Mass Index</subject><subject>cardiovascular diseases</subject><subject>chemiluminescence immunoassays</subject><subject>Dihydrofolate reductase</subject><subject>Double-Blind Method</subject><subject>Female</subject><subject>Ferredoxin-NADP Reductase - genetics</subject><subject>folic acid</subject><subject>Folic Acid - blood</subject><subject>Folic Acid Deficiency - blood</subject><subject>Folic Acid Deficiency - genetics</subject><subject>genotype</subject><subject>Genotyping Techniques</subject><subject>Homocysteine</subject><subject>Homocysteine - metabolism</subject><subject>hospitals</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Incidence</subject><subject>Laboratories</subject><subject>Linear Models</subject><subject>Male</subject><subject>Metabolism</subject><subject>methionine synthase</subject><subject>methylenetetrahydrofolate reductase</subject><subject>Methylenetetrahydrofolate Reductase (NADPH2) - genetics</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>patients</subject><subject>Polymerase Chain Reaction</subject><subject>Polymorphism</subject><subject>Polymorphism, Restriction Fragment Length</subject><subject>Polymorphism, Single Nucleotide</subject><subject>restriction fragment length polymorphism</subject><subject>Vitamin B</subject><subject>vitamin B deficiency</subject><issn>2072-6643</issn><issn>2072-6643</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqNks9u1DAQxiMEolXpgRdAlri0Egv-k7HjC1K1dHeLWoGq5Rx5nTHrksRLnFTKS_DMdbRlVTjVF88389Mne_Rl2VtGPwqh6ad2ULQAQcWL7JhTxWdS5uLlk_ooO43xjk5HUSXF6-yIS54mnB5nf1ahCXaMPfoWyQ32ZhNqHxuyxKS_h3psQrfbpk4kZzfr1eKWzKVS6w9kLy4Y18V8UqnmCuSSmLaaZNJSLs_J1-Dbvh7JZY33pkfSb5Hc-viLBEcWoZ5aX9B567G145vslTN1xNPH-yT7sbhcz1ez62_Lq_nF9cyCgH6mneKKgy64shyoZhY2mknFnMklQiEq4ZyVwCpRgNIb4VQFRmtAAIkOxUn2ee-7GzYNVhbbvjN1uet8Y7qxDMaX_05avy1_hvsyBwCW82Rw9mjQhd8Dxr5sfLRY16bFMMSS80IWCtQzUKZkeqRiTDwDpbkAJmByff8feheGrk1LSxTXnClVyESd7ynbhRg7dIcvMlpO8SkP8Unsu6c7OZB_wyIeAFHIudY</recordid><startdate>20150810</startdate><enddate>20150810</enddate><creator>Li, Wen-Xing</creator><creator>Dai, Shao-Xing</creator><creator>Zheng, Jun-Juan</creator><creator>Liu, Jia-Qian</creator><creator>Huang, Jing-Fei</creator><general>MDPI AG</general><general>MDPI</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>3V.</scope><scope>7TS</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope></search><sort><creationdate>20150810</creationdate><title>Homocysteine Metabolism Gene Polymorphisms (MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) Jointly Elevate the Risk of Folate Deficiency</title><author>Li, Wen-Xing ; Dai, Shao-Xing ; Zheng, Jun-Juan ; Liu, Jia-Qian ; Huang, Jing-Fei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c535t-9f727259827c25091c5b91671fa46e583d3ffc651d38579b3f7d5a995e556efe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase - genetics</topic><topic>Adult</topic><topic>Aged</topic><topic>Asian Continental Ancestry Group - genetics</topic><topic>Blood Pressure</topic><topic>blood serum</topic><topic>Body Mass Index</topic><topic>cardiovascular diseases</topic><topic>chemiluminescence immunoassays</topic><topic>Dihydrofolate reductase</topic><topic>Double-Blind Method</topic><topic>Female</topic><topic>Ferredoxin-NADP Reductase - genetics</topic><topic>folic acid</topic><topic>Folic Acid - blood</topic><topic>Folic Acid Deficiency - blood</topic><topic>Folic Acid Deficiency - genetics</topic><topic>genotype</topic><topic>Genotyping Techniques</topic><topic>Homocysteine</topic><topic>Homocysteine - metabolism</topic><topic>hospitals</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Incidence</topic><topic>Laboratories</topic><topic>Linear Models</topic><topic>Male</topic><topic>Metabolism</topic><topic>methionine synthase</topic><topic>methylenetetrahydrofolate reductase</topic><topic>Methylenetetrahydrofolate Reductase (NADPH2) - genetics</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>patients</topic><topic>Polymerase Chain Reaction</topic><topic>Polymorphism</topic><topic>Polymorphism, Restriction Fragment Length</topic><topic>Polymorphism, Single Nucleotide</topic><topic>restriction fragment length polymorphism</topic><topic>Vitamin B</topic><topic>vitamin B deficiency</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Wen-Xing</creatorcontrib><creatorcontrib>Dai, Shao-Xing</creatorcontrib><creatorcontrib>Zheng, Jun-Juan</creatorcontrib><creatorcontrib>Liu, Jia-Qian</creatorcontrib><creatorcontrib>Huang, Jing-Fei</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Physical Education Index</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nutrients</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Wen-Xing</au><au>Dai, Shao-Xing</au><au>Zheng, Jun-Juan</au><au>Liu, Jia-Qian</au><au>Huang, Jing-Fei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Homocysteine Metabolism Gene Polymorphisms (MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) Jointly Elevate the Risk of Folate Deficiency</atitle><jtitle>Nutrients</jtitle><addtitle>Nutrients</addtitle><date>2015-08-10</date><risdate>2015</risdate><volume>7</volume><issue>8</issue><spage>6670</spage><epage>6687</epage><pages>6670-6687</pages><issn>2072-6643</issn><eissn>2072-6643</eissn><abstract>Folate deficiency is strongly associated with cardiovascular disease. We aimed to explore the joint effect of the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, methionine synthase (MTR) A2756G, and methionine synthase reductase (MTRR) A66G polymorphisms on folate deficiency in a Chinese hypertensive population. A total of 480 subjects aged 28-75 were enrolled in this study from September 2005-December 2005 from six hospitals in different Chinese regions. Known genotypes were detected by PCR-RFLP methods and serum folate was measured by chemiluminescence immunoassay. Our results showed that MTHFR 677TT and MTR 2756AG + GG were independently associated with a higher risk of folate deficiency (TT vs. CC + CT, p < 0.001 and AG + GG vs. AA p = 0.030, respectively). However, the MTHFR A1298C mutation may confer protection by elevating the serum folate level (p = 0.025). Furthermore, patients carrying two or more risk genotypes showed higher odds of folate deficiency than null risk genotype carriers, especially those carrying four risk genotypes. These findings were verified by generalized multifactor dimensionality reduction (p = 0.0107) and a cumulative effects model (p = 0.001). The results of this study have shown that interactions among homocysteine metabolism gene polymorphisms lead to dramatic elevations in the folate deficiency risk.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>26266420</pmid><doi>10.3390/nu7085303</doi><tpages>18</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase - genetics Adult Aged Asian Continental Ancestry Group - genetics Blood Pressure blood serum Body Mass Index cardiovascular diseases chemiluminescence immunoassays Dihydrofolate reductase Double-Blind Method Female Ferredoxin-NADP Reductase - genetics folic acid Folic Acid - blood Folic Acid Deficiency - blood Folic Acid Deficiency - genetics genotype Genotyping Techniques Homocysteine Homocysteine - metabolism hospitals Humans Hypertension Incidence Laboratories Linear Models Male Metabolism methionine synthase methylenetetrahydrofolate reductase Methylenetetrahydrofolate Reductase (NADPH2) - genetics Middle Aged Mutation patients Polymerase Chain Reaction Polymorphism Polymorphism, Restriction Fragment Length Polymorphism, Single Nucleotide restriction fragment length polymorphism Vitamin B vitamin B deficiency |
| title | Homocysteine Metabolism Gene Polymorphisms (MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) Jointly Elevate the Risk of Folate Deficiency |
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