Patients with early onset of type 1 diabetes have significantly higher GG genotype at position 49 of the CTLA4 gene
Type 1 diabetes (T1D) is a complex autoimmune disease. Several genetic loci have been implicated in the susceptibility to this illness. Evaluated was the role of the CTLA4 exon 1 A49G polymorphism and its role as a risk factor for T1D in our population. DNA from 190 patients with T1D and their famil...
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| Veröffentlicht in: | Human immunology 2004-07, Vol.65 (7), p.719-724 |
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| creator | Zalloua, Pierre A. Abchee, Antoine Shbaklo, Hadia Zreik, Tony G. Terwedow, Henry Halaby, Georges Azar, Sami T. |
| description | Type 1 diabetes (T1D) is a complex autoimmune disease. Several genetic loci have been implicated in the susceptibility to this illness. Evaluated was the role of the CTLA4 exon 1 A49G polymorphism and its role as a risk factor for T1D in our population. DNA from 190 patients with T1D and their families and 96 control individuals were genotyped for CTLA4 exon 1 polymorphism and human leukocyte antigen (HLA)–DQB1*0201 and *0302 haplotypes by polymerase chain reaction (PCR) amplification–restriction enzyme analysis and PCR amplification that used sequence-specific primers, respectively. Patients were nonobese and |
| doi_str_mv | 10.1016/j.humimm.2004.04.007 |
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2 analysis and family-based association studies were performed and suggested the association of CTLA4 exon 1 G polymorphism with T1D (
p = 0.0229). Furthermore, in HLA-DQB1*0201–positive patients with T1D, the GG and AA genotypes were higher and lower, respectively, than those found in control individuals. This study suggests that CTLA4 is a candidate susceptibility gene for T1D.</description><identifier>ISSN: 0198-8859</identifier><identifier>EISSN: 1879-1166</identifier><identifier>DOI: 10.1016/j.humimm.2004.04.007</identifier><identifier>PMID: 15301861</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adolescent ; Adult ; Age of Onset ; Antigens, CD ; Antigens, Differentiation - genetics ; Child ; Child, Preschool ; CTLA-4 Antigen ; CTLA4 ; Data Interpretation, Statistical ; diabetes ; Diabetes Mellitus, Type 1 - ethnology ; Diabetes Mellitus, Type 1 - genetics ; DNA - genetics ; DNA - isolation & purification ; early onset ; Exons - genetics ; Female ; Gene Frequency - genetics ; Genetic Predisposition to Disease - genetics ; Genotype ; Heterozygote ; HLA-DQ Antigens - genetics ; HLA-DQ beta-Chains ; Homozygote ; Humans ; Lebanon ; Male ; MHC ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide - genetics ; SNP</subject><ispartof>Human immunology, 2004-07, Vol.65 (7), p.719-724</ispartof><rights>2004 American Society for Histocompatibility and Immunogenetics</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c389t-446532c3bf58ea7c08cf0702b5ada2eb3a40477ec7f17c4294160f8d36c6c2e83</citedby><cites>FETCH-LOGICAL-c389t-446532c3bf58ea7c08cf0702b5ada2eb3a40477ec7f17c4294160f8d36c6c2e83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0198885904001132$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15301861$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zalloua, Pierre A.</creatorcontrib><creatorcontrib>Abchee, Antoine</creatorcontrib><creatorcontrib>Shbaklo, Hadia</creatorcontrib><creatorcontrib>Zreik, Tony G.</creatorcontrib><creatorcontrib>Terwedow, Henry</creatorcontrib><creatorcontrib>Halaby, Georges</creatorcontrib><creatorcontrib>Azar, Sami T.</creatorcontrib><title>Patients with early onset of type 1 diabetes have significantly higher GG genotype at position 49 of the CTLA4 gene</title><title>Human immunology</title><addtitle>Hum Immunol</addtitle><description>Type 1 diabetes (T1D) is a complex autoimmune disease. Several genetic loci have been implicated in the susceptibility to this illness. Evaluated was the role of the CTLA4 exon 1 A49G polymorphism and its role as a risk factor for T1D in our population. DNA from 190 patients with T1D and their families and 96 control individuals were genotyped for CTLA4 exon 1 polymorphism and human leukocyte antigen (HLA)–DQB1*0201 and *0302 haplotypes by polymerase chain reaction (PCR) amplification–restriction enzyme analysis and PCR amplification that used sequence-specific primers, respectively. Patients were nonobese and <26 years old. The CTLA4 G allele was found to be more frequently present in patients with T1D (32.4%) as compared with its frequency in control individuals (24.5%). The GG genotype was also significantly higher among patients (12.6%) than in controls (4.2%). χ
2 analysis and family-based association studies were performed and suggested the association of CTLA4 exon 1 G polymorphism with T1D (
p = 0.0229). Furthermore, in HLA-DQB1*0201–positive patients with T1D, the GG and AA genotypes were higher and lower, respectively, than those found in control individuals. This study suggests that CTLA4 is a candidate susceptibility gene for T1D.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Age of Onset</subject><subject>Antigens, CD</subject><subject>Antigens, Differentiation - genetics</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>CTLA-4 Antigen</subject><subject>CTLA4</subject><subject>Data Interpretation, Statistical</subject><subject>diabetes</subject><subject>Diabetes Mellitus, Type 1 - ethnology</subject><subject>Diabetes Mellitus, Type 1 - genetics</subject><subject>DNA - genetics</subject><subject>DNA - isolation & purification</subject><subject>early onset</subject><subject>Exons - genetics</subject><subject>Female</subject><subject>Gene Frequency - genetics</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Genotype</subject><subject>Heterozygote</subject><subject>HLA-DQ Antigens - genetics</subject><subject>HLA-DQ beta-Chains</subject><subject>Homozygote</subject><subject>Humans</subject><subject>Lebanon</subject><subject>Male</subject><subject>MHC</subject><subject>Polymerase Chain Reaction</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>SNP</subject><issn>0198-8859</issn><issn>1879-1166</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFq4zAQhkXZpU27-wbLotPenGpsWZIvhRK2aSHQHrpnIcvjWCG2Uklpyduv3QR6a2FAl-__h9FHyC9gc2Agrjfzbt-7vp_njPH5NEyekRkoWWUAQnwjMwaVypQqqwtyGeOGjQST_JxcQFkwUAJmJD6Z5HBIkb651FE0YXugfoiYqG9pOuyQAm2cqTFhpJ15RRrdenCts2ZII9u5dYeBLpd0jYN_D5hEdz665PxAefXe0yFdPK9u-QThD_K9NduIP0_vFfl39_d5cZ-tHpcPi9tVZgtVpYxzURa5Leq2VGikZcq24wF5XZrG5FgXhjMuJVrZgrQ8rzgI1qqmEFbYHFVxRf4ce3fBv-wxJt27aHG7NQP6fdRCSFnmHL4EQUqmQBUjyI-gDT7GgK3eBdebcNDA9GRFb_TRip6s6GmYHGO_T_37usfmI3TSMAI3RwDH73h1GHS0oxWLjQtok268-3zDfza2n28</recordid><startdate>20040701</startdate><enddate>20040701</enddate><creator>Zalloua, Pierre A.</creator><creator>Abchee, Antoine</creator><creator>Shbaklo, Hadia</creator><creator>Zreik, Tony G.</creator><creator>Terwedow, Henry</creator><creator>Halaby, Georges</creator><creator>Azar, Sami T.</creator><general>Elsevier Inc</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>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20040701</creationdate><title>Patients with early onset of type 1 diabetes have significantly higher GG genotype at position 49 of the CTLA4 gene</title><author>Zalloua, Pierre A. ; Abchee, Antoine ; Shbaklo, Hadia ; Zreik, Tony G. ; Terwedow, Henry ; Halaby, Georges ; Azar, Sami T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c389t-446532c3bf58ea7c08cf0702b5ada2eb3a40477ec7f17c4294160f8d36c6c2e83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Age of Onset</topic><topic>Antigens, CD</topic><topic>Antigens, Differentiation - genetics</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>CTLA-4 Antigen</topic><topic>CTLA4</topic><topic>Data Interpretation, Statistical</topic><topic>diabetes</topic><topic>Diabetes Mellitus, Type 1 - ethnology</topic><topic>Diabetes Mellitus, Type 1 - genetics</topic><topic>DNA - genetics</topic><topic>DNA - isolation & purification</topic><topic>early onset</topic><topic>Exons - genetics</topic><topic>Female</topic><topic>Gene Frequency - genetics</topic><topic>Genetic Predisposition to Disease - genetics</topic><topic>Genotype</topic><topic>Heterozygote</topic><topic>HLA-DQ Antigens - genetics</topic><topic>HLA-DQ beta-Chains</topic><topic>Homozygote</topic><topic>Humans</topic><topic>Lebanon</topic><topic>Male</topic><topic>MHC</topic><topic>Polymerase Chain Reaction</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>SNP</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zalloua, Pierre A.</creatorcontrib><creatorcontrib>Abchee, Antoine</creatorcontrib><creatorcontrib>Shbaklo, Hadia</creatorcontrib><creatorcontrib>Zreik, Tony G.</creatorcontrib><creatorcontrib>Terwedow, Henry</creatorcontrib><creatorcontrib>Halaby, Georges</creatorcontrib><creatorcontrib>Azar, Sami T.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Human immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zalloua, Pierre A.</au><au>Abchee, Antoine</au><au>Shbaklo, Hadia</au><au>Zreik, Tony G.</au><au>Terwedow, Henry</au><au>Halaby, Georges</au><au>Azar, Sami T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Patients with early onset of type 1 diabetes have significantly higher GG genotype at position 49 of the CTLA4 gene</atitle><jtitle>Human immunology</jtitle><addtitle>Hum Immunol</addtitle><date>2004-07-01</date><risdate>2004</risdate><volume>65</volume><issue>7</issue><spage>719</spage><epage>724</epage><pages>719-724</pages><issn>0198-8859</issn><eissn>1879-1166</eissn><abstract>Type 1 diabetes (T1D) is a complex autoimmune disease. Several genetic loci have been implicated in the susceptibility to this illness. Evaluated was the role of the CTLA4 exon 1 A49G polymorphism and its role as a risk factor for T1D in our population. DNA from 190 patients with T1D and their families and 96 control individuals were genotyped for CTLA4 exon 1 polymorphism and human leukocyte antigen (HLA)–DQB1*0201 and *0302 haplotypes by polymerase chain reaction (PCR) amplification–restriction enzyme analysis and PCR amplification that used sequence-specific primers, respectively. Patients were nonobese and <26 years old. The CTLA4 G allele was found to be more frequently present in patients with T1D (32.4%) as compared with its frequency in control individuals (24.5%). The GG genotype was also significantly higher among patients (12.6%) than in controls (4.2%). χ
2 analysis and family-based association studies were performed and suggested the association of CTLA4 exon 1 G polymorphism with T1D (
p = 0.0229). Furthermore, in HLA-DQB1*0201–positive patients with T1D, the GG and AA genotypes were higher and lower, respectively, than those found in control individuals. This study suggests that CTLA4 is a candidate susceptibility gene for T1D.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>15301861</pmid><doi>10.1016/j.humimm.2004.04.007</doi><tpages>6</tpages></addata></record> |
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| subjects | Adolescent Adult Age of Onset Antigens, CD Antigens, Differentiation - genetics Child Child, Preschool CTLA-4 Antigen CTLA4 Data Interpretation, Statistical diabetes Diabetes Mellitus, Type 1 - ethnology Diabetes Mellitus, Type 1 - genetics DNA - genetics DNA - isolation & purification early onset Exons - genetics Female Gene Frequency - genetics Genetic Predisposition to Disease - genetics Genotype Heterozygote HLA-DQ Antigens - genetics HLA-DQ beta-Chains Homozygote Humans Lebanon Male MHC Polymerase Chain Reaction Polymorphism, Single Nucleotide - genetics SNP |
| title | Patients with early onset of type 1 diabetes have significantly higher GG genotype at position 49 of the CTLA4 gene |
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