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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Veröffentlicht in:The journal of gene medicine 2021-08, Vol.23 (8), p.e3347-n/a, Article 3347
Hauptverfasser: 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
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container_issue 8
container_start_page e3347
container_title The journal of gene medicine
container_volume 23
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
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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 &amp; 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 &amp; 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 &amp; 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 &amp; Biomedicine</subject><subject>Male</subject><subject>Mass spectroscopy</subject><subject>Medicine, Research &amp; 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 &amp; Experimental Medicine</subject><subject>Science &amp; 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 &amp; 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 &amp; 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 &amp; Biomedicine</topic><topic>Male</topic><topic>Mass spectroscopy</topic><topic>Medicine, Research &amp; 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 &amp; Experimental Medicine</topic><topic>Science &amp; 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 &amp; 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 &amp; 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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