Interaction analysis of gene variants related to one‐carbon metabolism with chronic hepatitis B infection in Chinese patients
Background The risk of chronic hepatitis B (CHB) infection is influenced by aberrant DNA methylation and altered nucleotide synthesis and repair, possibly caused by polymorphic variants in one‐carbon metabolism genes. In the present study, we investigated the relationship between polymorphisms belon...
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creator | Sun, Yao‐Hui Gao, Jie Liu, Xu‐Dong Tang, Hong‐Wei Cao, Sheng‐Li Zhang, Jia‐Kai Wen, Pei‐Hao Wang, Zhi‐Hui Li, Jie Guo, Wen‐Zhi Zhang, Shui‐Jun |
description | Background
The risk of chronic hepatitis B (CHB) infection is influenced by aberrant DNA methylation and altered nucleotide synthesis and repair, possibly caused by polymorphic variants in one‐carbon metabolism genes. In the present study, we investigated the relationship between polymorphisms belonging to the one‐carbon metabolic pathway and CHB infection.
Methods
A case–control study using 230 CHB patients and 234 unrelated healthy controls was carried out to assess the genetic association of 24 single nucleotide polymorphisins (SNPs) determined by mass spectrometry.
Results
Three SNPs, comprising rs10717122 and rs2229717 in serine hydroxymethyltransferase1/2 (SHMT2) and rs585800 in betaine‐homocysteine S‐methyltransferase (BHMT), were associated with the risk of CHB. Patients with DEL allele, DEL.DEL and DEL.T genotypes of rs10717122 had a 1.40‐, 2.00‐ and 1.83‐fold increased risk for CHB, respectively. Cases inheriting TA genotype of rs585800 had a 2.19‐fold risk for CHB infection. The T allele of rs2229717 was less represented in the CHB cases (odds ratio = 0.66, 95% confidence interval = 0.48–0.92). The T allele of rs2229717 was less in patients with a low hepatitis B virus‐DNA level compared to the control group (odds ratio = 0.49, 95% confidence interval = 0.25–0.97) and TT genotype of rs2229717 had a significant correlation with hepatitis B surface antigen level (p = 0.0195). Further gene–gene interaction analysis showed that subjects carrying the rs10717122 DEL.DEL/DEL.T and rs585800 TT/TA genotypes had a 2.74‐fold increased risk of CHB.
Conclusions
The results of the present study suggest that rs10717122, rs585800 and rs2229717 and gene–gene interactions of rs10717122 and rs585800 affect the outcome of CHB infection, at the same time as indicating their usefulness as a predictive and diagnostic biomarker of CHB infection.
The risk of chronic hepatitis B (CHB) infection is influenced by aberrant DNA methylation and altered nucleotide synthesis and repair, possibly caused by polymorphic variants in one‐carbon metabolism (OCM) genes. The OCM and polymorphism frequency distribution of multiple related enzyme genes is illustrated. Genotype frequencies in the CHB patients and control groups were similar for 24 candidate singe nucleotide polymorphisms of 10 OCM genes, with the exception of two polymorphisms of serine hydroxymethyltransferase1/2 (SHMT2) (rs10717122 and rs2229717) and one polymorphism of betaine‐homocysteine S‐methyltransferase (BHMT) (r |
doi_str_mv | 10.1002/jgm.3347 |
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fullrecord | <record><control><sourceid>proquest_webof</sourceid><recordid>TN_cdi_webofscience_primary_000648691600001</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2518225017</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3497-2694062cd3b3347818bda2260460080c7b64a0326715859f67988155c70512aa3</originalsourceid><addsrcrecordid>eNqNkc2KFDEUhQtRnHEUfAIJuBGkxvxVfpZO4YwjI24U3BWp9K3pNFVJm6QceuU8gs_ok5iy2xEEwVUu5LuHc8-pqqcEnxKM6avN9XTKGJf3qmPSUFJT2vD7ZcZa11yrz0fVo5Q2GBOplH5YHTGmNMecH1ffLn2GaGx2wSPjzbhLLqEwoGvwgL6a6IzPCUUYTYYVygEFDz9uv1sT-7IxQTZ9GF2a0I3La2TXMXhn0Rq2JrtcpM6Q8wPs9Z1H7dp5SICWbyjKj6sHgxkTPDm8J9Wn8zcf27f11YeLy_b1VW0Z17KmovgV1K5Yv9ypiOpXhlKBucBYYSt7wQ1mVEjSqEYPQmqlSNNYiRtCjWEn1Yu97jaGLzOk3E0uWRhH4yHMqaMNUSW1klBBn_-FbsIcSzQL1UjCJcPij6CNIaUIQ7eNbjJx1xHcLaV0pZRuMVvQZwfBuZ9gdQf-bqEAL_fADfRhSLYkY-EOwxgLroQm5dRSYaHV_9Oty2bJvg2zz2W1Pqy6EXb_dNy9u3j_y_lPJsW2dA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2557147306</pqid></control><display><type>article</type><title>Interaction analysis of gene variants related to one‐carbon metabolism with chronic hepatitis B infection in Chinese patients</title><source>MEDLINE</source><source>Access via Wiley Online Library</source><source>Web of Science - Science Citation Index Expanded - 2021<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /></source><creator>Sun, Yao‐Hui ; Gao, Jie ; Liu, Xu‐Dong ; Tang, Hong‐Wei ; Cao, Sheng‐Li ; Zhang, Jia‐Kai ; Wen, Pei‐Hao ; Wang, Zhi‐Hui ; Li, Jie ; Guo, Wen‐Zhi ; Zhang, Shui‐Jun</creator><creatorcontrib>Sun, Yao‐Hui ; Gao, Jie ; Liu, Xu‐Dong ; Tang, Hong‐Wei ; Cao, Sheng‐Li ; Zhang, Jia‐Kai ; Wen, Pei‐Hao ; Wang, Zhi‐Hui ; Li, Jie ; Guo, Wen‐Zhi ; Zhang, Shui‐Jun</creatorcontrib><description>Background
The risk of chronic hepatitis B (CHB) infection is influenced by aberrant DNA methylation and altered nucleotide synthesis and repair, possibly caused by polymorphic variants in one‐carbon metabolism genes. In the present study, we investigated the relationship between polymorphisms belonging to the one‐carbon metabolic pathway and CHB infection.
Methods
A case–control study using 230 CHB patients and 234 unrelated healthy controls was carried out to assess the genetic association of 24 single nucleotide polymorphisins (SNPs) determined by mass spectrometry.
Results
Three SNPs, comprising rs10717122 and rs2229717 in serine hydroxymethyltransferase1/2 (SHMT2) and rs585800 in betaine‐homocysteine S‐methyltransferase (BHMT), were associated with the risk of CHB. Patients with DEL allele, DEL.DEL and DEL.T genotypes of rs10717122 had a 1.40‐, 2.00‐ and 1.83‐fold increased risk for CHB, respectively. Cases inheriting TA genotype of rs585800 had a 2.19‐fold risk for CHB infection. The T allele of rs2229717 was less represented in the CHB cases (odds ratio = 0.66, 95% confidence interval = 0.48–0.92). The T allele of rs2229717 was less in patients with a low hepatitis B virus‐DNA level compared to the control group (odds ratio = 0.49, 95% confidence interval = 0.25–0.97) and TT genotype of rs2229717 had a significant correlation with hepatitis B surface antigen level (p = 0.0195). Further gene–gene interaction analysis showed that subjects carrying the rs10717122 DEL.DEL/DEL.T and rs585800 TT/TA genotypes had a 2.74‐fold increased risk of CHB.
Conclusions
The results of the present study suggest that rs10717122, rs585800 and rs2229717 and gene–gene interactions of rs10717122 and rs585800 affect the outcome of CHB infection, at the same time as indicating their usefulness as a predictive and diagnostic biomarker of CHB infection.
The risk of chronic hepatitis B (CHB) infection is influenced by aberrant DNA methylation and altered nucleotide synthesis and repair, possibly caused by polymorphic variants in one‐carbon metabolism (OCM) genes. The OCM and polymorphism frequency distribution of multiple related enzyme genes is illustrated. Genotype frequencies in the CHB patients and control groups were similar for 24 candidate singe nucleotide polymorphisms of 10 OCM genes, with the exception of two polymorphisms of serine hydroxymethyltransferase1/2 (SHMT2) (rs10717122 and rs2229717) and one polymorphism of betaine‐homocysteine S‐methyltransferase (BHMT) (rs585800).</description><identifier>ISSN: 1099-498X</identifier><identifier>EISSN: 1521-2254</identifier><identifier>DOI: 10.1002/jgm.3347</identifier><identifier>PMID: 33894044</identifier><language>eng</language><publisher>HOBOKEN: Wiley</publisher><subject><![CDATA[5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase - genetics ; Adenosylhomocysteinase - genetics ; Adult ; Alleles ; Asians - genetics ; Betaine ; Betaine-homocysteine S-methyltransferase ; Betaine-Homocysteine S-Methyltransferase - genetics ; Biotechnology & Applied Microbiology ; Carbon ; Carbon - metabolism ; Case-Control Studies ; chronic hepatitis B infection ; Chronic infection ; Confidence intervals ; Deoxyribonucleic acid ; DNA ; DNA methylation ; DNA Modification Methylases - genetics ; DNA Repair Enzymes - genetics ; DNA viruses ; Female ; Gene therapy ; Genetic Predisposition to Disease ; Genetics & Heredity ; Glycine Hydroxymethyltransferase - genetics ; Glycine N-Methyltransferase - genetics ; Hepatitis B ; Hepatitis B surface antigen ; Hepatitis B, Chronic - genetics ; Hepatitis B, Chronic - metabolism ; Homocysteine ; Humans ; Infections ; Life Sciences & Biomedicine ; Male ; Mass spectroscopy ; Medicine, Research & Experimental ; Metabolic pathways ; Metabolism ; Methionine Adenosyltransferase - genetics ; Methylenetetrahydrofolate Reductase (NADPH2) - genetics ; Methyltransferase ; Middle Aged ; one‐carbon metabolism ; Polymorphism, Single Nucleotide ; Research & Experimental Medicine ; Science & Technology ; Serine ; Single-nucleotide polymorphism ; SNP ; Tumor Suppressor Proteins - genetics]]></subject><ispartof>The journal of gene medicine, 2021-08, Vol.23 (8), p.e3347-n/a, Article 3347</ispartof><rights>2021 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>2</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000648691600001</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c3497-2694062cd3b3347818bda2260460080c7b64a0326715859f67988155c70512aa3</citedby><cites>FETCH-LOGICAL-c3497-2694062cd3b3347818bda2260460080c7b64a0326715859f67988155c70512aa3</cites><orcidid>0000-0003-4893-4331</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjgm.3347$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjgm.3347$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,27928,27929,39262,45578,45579</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33894044$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sun, Yao‐Hui</creatorcontrib><creatorcontrib>Gao, Jie</creatorcontrib><creatorcontrib>Liu, Xu‐Dong</creatorcontrib><creatorcontrib>Tang, Hong‐Wei</creatorcontrib><creatorcontrib>Cao, Sheng‐Li</creatorcontrib><creatorcontrib>Zhang, Jia‐Kai</creatorcontrib><creatorcontrib>Wen, Pei‐Hao</creatorcontrib><creatorcontrib>Wang, Zhi‐Hui</creatorcontrib><creatorcontrib>Li, Jie</creatorcontrib><creatorcontrib>Guo, Wen‐Zhi</creatorcontrib><creatorcontrib>Zhang, Shui‐Jun</creatorcontrib><title>Interaction analysis of gene variants related to one‐carbon metabolism with chronic hepatitis B infection in Chinese patients</title><title>The journal of gene medicine</title><addtitle>J GENE MED</addtitle><addtitle>J Gene Med</addtitle><description>Background
The risk of chronic hepatitis B (CHB) infection is influenced by aberrant DNA methylation and altered nucleotide synthesis and repair, possibly caused by polymorphic variants in one‐carbon metabolism genes. In the present study, we investigated the relationship between polymorphisms belonging to the one‐carbon metabolic pathway and CHB infection.
Methods
A case–control study using 230 CHB patients and 234 unrelated healthy controls was carried out to assess the genetic association of 24 single nucleotide polymorphisins (SNPs) determined by mass spectrometry.
Results
Three SNPs, comprising rs10717122 and rs2229717 in serine hydroxymethyltransferase1/2 (SHMT2) and rs585800 in betaine‐homocysteine S‐methyltransferase (BHMT), were associated with the risk of CHB. Patients with DEL allele, DEL.DEL and DEL.T genotypes of rs10717122 had a 1.40‐, 2.00‐ and 1.83‐fold increased risk for CHB, respectively. Cases inheriting TA genotype of rs585800 had a 2.19‐fold risk for CHB infection. The T allele of rs2229717 was less represented in the CHB cases (odds ratio = 0.66, 95% confidence interval = 0.48–0.92). The T allele of rs2229717 was less in patients with a low hepatitis B virus‐DNA level compared to the control group (odds ratio = 0.49, 95% confidence interval = 0.25–0.97) and TT genotype of rs2229717 had a significant correlation with hepatitis B surface antigen level (p = 0.0195). Further gene–gene interaction analysis showed that subjects carrying the rs10717122 DEL.DEL/DEL.T and rs585800 TT/TA genotypes had a 2.74‐fold increased risk of CHB.
Conclusions
The results of the present study suggest that rs10717122, rs585800 and rs2229717 and gene–gene interactions of rs10717122 and rs585800 affect the outcome of CHB infection, at the same time as indicating their usefulness as a predictive and diagnostic biomarker of CHB infection.
The risk of chronic hepatitis B (CHB) infection is influenced by aberrant DNA methylation and altered nucleotide synthesis and repair, possibly caused by polymorphic variants in one‐carbon metabolism (OCM) genes. The OCM and polymorphism frequency distribution of multiple related enzyme genes is illustrated. Genotype frequencies in the CHB patients and control groups were similar for 24 candidate singe nucleotide polymorphisms of 10 OCM genes, with the exception of two polymorphisms of serine hydroxymethyltransferase1/2 (SHMT2) (rs10717122 and rs2229717) and one polymorphism of betaine‐homocysteine S‐methyltransferase (BHMT) (rs585800).</description><subject>5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase - genetics</subject><subject>Adenosylhomocysteinase - genetics</subject><subject>Adult</subject><subject>Alleles</subject><subject>Asians - genetics</subject><subject>Betaine</subject><subject>Betaine-homocysteine S-methyltransferase</subject><subject>Betaine-Homocysteine S-Methyltransferase - genetics</subject><subject>Biotechnology & Applied Microbiology</subject><subject>Carbon</subject><subject>Carbon - metabolism</subject><subject>Case-Control Studies</subject><subject>chronic hepatitis B infection</subject><subject>Chronic infection</subject><subject>Confidence intervals</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>DNA Modification Methylases - genetics</subject><subject>DNA Repair Enzymes - genetics</subject><subject>DNA viruses</subject><subject>Female</subject><subject>Gene therapy</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetics & Heredity</subject><subject>Glycine Hydroxymethyltransferase - genetics</subject><subject>Glycine N-Methyltransferase - genetics</subject><subject>Hepatitis B</subject><subject>Hepatitis B surface antigen</subject><subject>Hepatitis B, Chronic - genetics</subject><subject>Hepatitis B, Chronic - metabolism</subject><subject>Homocysteine</subject><subject>Humans</subject><subject>Infections</subject><subject>Life Sciences & Biomedicine</subject><subject>Male</subject><subject>Mass spectroscopy</subject><subject>Medicine, Research & Experimental</subject><subject>Metabolic pathways</subject><subject>Metabolism</subject><subject>Methionine Adenosyltransferase - genetics</subject><subject>Methylenetetrahydrofolate Reductase (NADPH2) - genetics</subject><subject>Methyltransferase</subject><subject>Middle Aged</subject><subject>one‐carbon metabolism</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Research & Experimental Medicine</subject><subject>Science & Technology</subject><subject>Serine</subject><subject>Single-nucleotide polymorphism</subject><subject>SNP</subject><subject>Tumor Suppressor Proteins - genetics</subject><issn>1099-498X</issn><issn>1521-2254</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>HGBXW</sourceid><sourceid>EIF</sourceid><recordid>eNqNkc2KFDEUhQtRnHEUfAIJuBGkxvxVfpZO4YwjI24U3BWp9K3pNFVJm6QceuU8gs_ok5iy2xEEwVUu5LuHc8-pqqcEnxKM6avN9XTKGJf3qmPSUFJT2vD7ZcZa11yrz0fVo5Q2GBOplH5YHTGmNMecH1ffLn2GaGx2wSPjzbhLLqEwoGvwgL6a6IzPCUUYTYYVygEFDz9uv1sT-7IxQTZ9GF2a0I3La2TXMXhn0Rq2JrtcpM6Q8wPs9Z1H7dp5SICWbyjKj6sHgxkTPDm8J9Wn8zcf27f11YeLy_b1VW0Z17KmovgV1K5Yv9ypiOpXhlKBucBYYSt7wQ1mVEjSqEYPQmqlSNNYiRtCjWEn1Yu97jaGLzOk3E0uWRhH4yHMqaMNUSW1klBBn_-FbsIcSzQL1UjCJcPij6CNIaUIQ7eNbjJx1xHcLaV0pZRuMVvQZwfBuZ9gdQf-bqEAL_fADfRhSLYkY-EOwxgLroQm5dRSYaHV_9Oty2bJvg2zz2W1Pqy6EXb_dNy9u3j_y_lPJsW2dA</recordid><startdate>202108</startdate><enddate>202108</enddate><creator>Sun, Yao‐Hui</creator><creator>Gao, Jie</creator><creator>Liu, Xu‐Dong</creator><creator>Tang, Hong‐Wei</creator><creator>Cao, Sheng‐Li</creator><creator>Zhang, Jia‐Kai</creator><creator>Wen, Pei‐Hao</creator><creator>Wang, Zhi‐Hui</creator><creator>Li, Jie</creator><creator>Guo, Wen‐Zhi</creator><creator>Zhang, Shui‐Jun</creator><general>Wiley</general><general>Wiley Periodicals Inc</general><scope>BLEPL</scope><scope>DTL</scope><scope>HGBXW</scope><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>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-4893-4331</orcidid></search><sort><creationdate>202108</creationdate><title>Interaction analysis of gene variants related to one‐carbon metabolism with chronic hepatitis B infection in Chinese patients</title><author>Sun, Yao‐Hui ; Gao, Jie ; Liu, Xu‐Dong ; Tang, Hong‐Wei ; Cao, Sheng‐Li ; Zhang, Jia‐Kai ; Wen, Pei‐Hao ; Wang, Zhi‐Hui ; Li, Jie ; Guo, Wen‐Zhi ; Zhang, Shui‐Jun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3497-2694062cd3b3347818bda2260460080c7b64a0326715859f67988155c70512aa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase - genetics</topic><topic>Adenosylhomocysteinase - genetics</topic><topic>Adult</topic><topic>Alleles</topic><topic>Asians - genetics</topic><topic>Betaine</topic><topic>Betaine-homocysteine S-methyltransferase</topic><topic>Betaine-Homocysteine S-Methyltransferase - genetics</topic><topic>Biotechnology & Applied Microbiology</topic><topic>Carbon</topic><topic>Carbon - metabolism</topic><topic>Case-Control Studies</topic><topic>chronic hepatitis B infection</topic><topic>Chronic infection</topic><topic>Confidence intervals</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA methylation</topic><topic>DNA Modification Methylases - genetics</topic><topic>DNA Repair Enzymes - genetics</topic><topic>DNA viruses</topic><topic>Female</topic><topic>Gene therapy</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetics & Heredity</topic><topic>Glycine Hydroxymethyltransferase - genetics</topic><topic>Glycine N-Methyltransferase - genetics</topic><topic>Hepatitis B</topic><topic>Hepatitis B surface antigen</topic><topic>Hepatitis B, Chronic - genetics</topic><topic>Hepatitis B, Chronic - metabolism</topic><topic>Homocysteine</topic><topic>Humans</topic><topic>Infections</topic><topic>Life Sciences & Biomedicine</topic><topic>Male</topic><topic>Mass spectroscopy</topic><topic>Medicine, Research & Experimental</topic><topic>Metabolic pathways</topic><topic>Metabolism</topic><topic>Methionine Adenosyltransferase - genetics</topic><topic>Methylenetetrahydrofolate Reductase (NADPH2) - genetics</topic><topic>Methyltransferase</topic><topic>Middle Aged</topic><topic>one‐carbon metabolism</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Research & Experimental Medicine</topic><topic>Science & Technology</topic><topic>Serine</topic><topic>Single-nucleotide polymorphism</topic><topic>SNP</topic><topic>Tumor Suppressor Proteins - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sun, Yao‐Hui</creatorcontrib><creatorcontrib>Gao, Jie</creatorcontrib><creatorcontrib>Liu, Xu‐Dong</creatorcontrib><creatorcontrib>Tang, Hong‐Wei</creatorcontrib><creatorcontrib>Cao, Sheng‐Li</creatorcontrib><creatorcontrib>Zhang, Jia‐Kai</creatorcontrib><creatorcontrib>Wen, Pei‐Hao</creatorcontrib><creatorcontrib>Wang, Zhi‐Hui</creatorcontrib><creatorcontrib>Li, Jie</creatorcontrib><creatorcontrib>Guo, Wen‐Zhi</creatorcontrib><creatorcontrib>Zhang, Shui‐Jun</creatorcontrib><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Web of Science - Science Citation Index Expanded - 2021</collection><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>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The journal of gene medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sun, Yao‐Hui</au><au>Gao, Jie</au><au>Liu, Xu‐Dong</au><au>Tang, Hong‐Wei</au><au>Cao, Sheng‐Li</au><au>Zhang, Jia‐Kai</au><au>Wen, Pei‐Hao</au><au>Wang, Zhi‐Hui</au><au>Li, Jie</au><au>Guo, Wen‐Zhi</au><au>Zhang, Shui‐Jun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interaction analysis of gene variants related to one‐carbon metabolism with chronic hepatitis B infection in Chinese patients</atitle><jtitle>The journal of gene medicine</jtitle><stitle>J GENE MED</stitle><addtitle>J Gene Med</addtitle><date>2021-08</date><risdate>2021</risdate><volume>23</volume><issue>8</issue><spage>e3347</spage><epage>n/a</epage><pages>e3347-n/a</pages><artnum>3347</artnum><issn>1099-498X</issn><eissn>1521-2254</eissn><abstract>Background
The risk of chronic hepatitis B (CHB) infection is influenced by aberrant DNA methylation and altered nucleotide synthesis and repair, possibly caused by polymorphic variants in one‐carbon metabolism genes. In the present study, we investigated the relationship between polymorphisms belonging to the one‐carbon metabolic pathway and CHB infection.
Methods
A case–control study using 230 CHB patients and 234 unrelated healthy controls was carried out to assess the genetic association of 24 single nucleotide polymorphisins (SNPs) determined by mass spectrometry.
Results
Three SNPs, comprising rs10717122 and rs2229717 in serine hydroxymethyltransferase1/2 (SHMT2) and rs585800 in betaine‐homocysteine S‐methyltransferase (BHMT), were associated with the risk of CHB. Patients with DEL allele, DEL.DEL and DEL.T genotypes of rs10717122 had a 1.40‐, 2.00‐ and 1.83‐fold increased risk for CHB, respectively. Cases inheriting TA genotype of rs585800 had a 2.19‐fold risk for CHB infection. The T allele of rs2229717 was less represented in the CHB cases (odds ratio = 0.66, 95% confidence interval = 0.48–0.92). The T allele of rs2229717 was less in patients with a low hepatitis B virus‐DNA level compared to the control group (odds ratio = 0.49, 95% confidence interval = 0.25–0.97) and TT genotype of rs2229717 had a significant correlation with hepatitis B surface antigen level (p = 0.0195). Further gene–gene interaction analysis showed that subjects carrying the rs10717122 DEL.DEL/DEL.T and rs585800 TT/TA genotypes had a 2.74‐fold increased risk of CHB.
Conclusions
The results of the present study suggest that rs10717122, rs585800 and rs2229717 and gene–gene interactions of rs10717122 and rs585800 affect the outcome of CHB infection, at the same time as indicating their usefulness as a predictive and diagnostic biomarker of CHB infection.
The risk of chronic hepatitis B (CHB) infection is influenced by aberrant DNA methylation and altered nucleotide synthesis and repair, possibly caused by polymorphic variants in one‐carbon metabolism (OCM) genes. The OCM and polymorphism frequency distribution of multiple related enzyme genes is illustrated. Genotype frequencies in the CHB patients and control groups were similar for 24 candidate singe nucleotide polymorphisms of 10 OCM genes, with the exception of two polymorphisms of serine hydroxymethyltransferase1/2 (SHMT2) (rs10717122 and rs2229717) and one polymorphism of betaine‐homocysteine S‐methyltransferase (BHMT) (rs585800).</abstract><cop>HOBOKEN</cop><pub>Wiley</pub><pmid>33894044</pmid><doi>10.1002/jgm.3347</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0003-4893-4331</orcidid></addata></record> |
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subjects | 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase - genetics Adenosylhomocysteinase - genetics Adult Alleles Asians - genetics Betaine Betaine-homocysteine S-methyltransferase Betaine-Homocysteine S-Methyltransferase - genetics Biotechnology & Applied Microbiology Carbon Carbon - metabolism Case-Control Studies chronic hepatitis B infection Chronic infection Confidence intervals Deoxyribonucleic acid DNA DNA methylation DNA Modification Methylases - genetics DNA Repair Enzymes - genetics DNA viruses Female Gene therapy Genetic Predisposition to Disease Genetics & Heredity Glycine Hydroxymethyltransferase - genetics Glycine N-Methyltransferase - genetics Hepatitis B Hepatitis B surface antigen Hepatitis B, Chronic - genetics Hepatitis B, Chronic - metabolism Homocysteine Humans Infections Life Sciences & Biomedicine Male Mass spectroscopy Medicine, Research & Experimental Metabolic pathways Metabolism Methionine Adenosyltransferase - genetics Methylenetetrahydrofolate Reductase (NADPH2) - genetics Methyltransferase Middle Aged one‐carbon metabolism Polymorphism, Single Nucleotide Research & Experimental Medicine Science & Technology Serine Single-nucleotide polymorphism SNP Tumor Suppressor Proteins - genetics |
title | Interaction analysis of gene variants related to one‐carbon metabolism with chronic hepatitis B infection in Chinese patients |
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