New susceptibility and resistance HLA-DP alleles to HBV-related diseases identified by a trans-ethnic association study in Asia
Previous studies have revealed the association between SNPs located on human leukocyte antigen (HLA) class II genes, including HLA-DP and HLA-DQ, and chronic hepatitis B virus (HBV) infection, mainly in Asian populations. HLA-DP alleles or haplotypes associated with chronic HBV infection or disease...
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| creator | Nishida, Nao Sawai, Hiromi Kashiwase, Koichi Minami, Mutsuhiko Sugiyama, Masaya Seto, Wai-Kay Yuen, Man-Fung Posuwan, Nawarat Poovorawan, Yong Ahn, Sang Hoon Han, Kwang-Hyub Matsuura, Kentaro Tanaka, Yasuhito Kurosaki, Masayuki Asahina, Yasuhiro Izumi, Namiki Kang, Jong-Hon Hige, Shuhei Ide, Tatsuya Yamamoto, Kazuhide Sakaida, Isao Murawaki, Yoshikazu Itoh, Yoshito Tamori, Akihiro Orito, Etsuro Hiasa, Yoichi Honda, Masao Kaneko, Shuichi Mita, Eiji Suzuki, Kazuyuki Hino, Keisuke Tanaka, Eiji Mochida, Satoshi Watanabe, Masaaki Eguchi, Yuichiro Masaki, Naohiko Murata, Kazumoto Korenaga, Masaaki Mawatari, Yoriko Ohashi, Jun Kawashima, Minae Tokunaga, Katsushi Mizokami, Masashi |
| description | Previous studies have revealed the association between SNPs located on human leukocyte antigen (HLA) class II genes, including HLA-DP and HLA-DQ, and chronic hepatitis B virus (HBV) infection, mainly in Asian populations. HLA-DP alleles or haplotypes associated with chronic HBV infection or disease progression have not been fully identified in Asian populations. We performed trans-ethnic association analyses of HLA-DPA1, HLA-DPB1 alleles and haplotypes with hepatitis B virus infection and disease progression among Asian populations comprising Japanese, Korean, Hong Kong, and Thai subjects. To assess the association between HLA-DP and chronic HBV infection and disease progression, we conducted high-resolution (4-digit) HLA-DPA1 and HLA-DPB1 genotyping in a total of 3,167 samples, including HBV patients, HBV-resolved individuals and healthy controls. Trans-ethnic association analyses among Asian populations identified a new risk allele HLA-DPB1*09 ∶ 01 (P = 1.36 × 10(-6); OR= 1.97; 95% CI, 1.50-2.59) and a new protective allele DPB1*02 ∶ 01 (P = 5.22 × 10(-6); OR = 0.68; 95% CI, 0.58-0.81) to chronic HBV infection, in addition to the previously reported alleles. Moreover, DPB1*02 ∶ 01 was also associated with a decreased risk of disease progression in chronic HBV patients among Asian populations (P = 1.55 × 10(-7); OR = 0.50; 95% CI, 0.39-0.65). Trans-ethnic association analyses identified Asian-specific associations of HLA-DP alleles and haplotypes with HBV infection or disease progression. The present findings will serve as a base for future functional studies of HLA-DP molecules in order to understand the pathogenesis of HBV infection and the development of hepatocellular carcinoma. |
| doi_str_mv | 10.1371/journal.pone.0086449 |
| format | Article |
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HLA-DP alleles or haplotypes associated with chronic HBV infection or disease progression have not been fully identified in Asian populations. We performed trans-ethnic association analyses of HLA-DPA1, HLA-DPB1 alleles and haplotypes with hepatitis B virus infection and disease progression among Asian populations comprising Japanese, Korean, Hong Kong, and Thai subjects. To assess the association between HLA-DP and chronic HBV infection and disease progression, we conducted high-resolution (4-digit) HLA-DPA1 and HLA-DPB1 genotyping in a total of 3,167 samples, including HBV patients, HBV-resolved individuals and healthy controls. Trans-ethnic association analyses among Asian populations identified a new risk allele HLA-DPB1*09 ∶ 01 (P = 1.36 × 10(-6); OR= 1.97; 95% CI, 1.50-2.59) and a new protective allele DPB1*02 ∶ 01 (P = 5.22 × 10(-6); OR = 0.68; 95% CI, 0.58-0.81) to chronic HBV infection, in addition to the previously reported alleles. Moreover, DPB1*02 ∶ 01 was also associated with a decreased risk of disease progression in chronic HBV patients among Asian populations (P = 1.55 × 10(-7); OR = 0.50; 95% CI, 0.39-0.65). Trans-ethnic association analyses identified Asian-specific associations of HLA-DP alleles and haplotypes with HBV infection or disease progression. The present findings will serve as a base for future functional studies of HLA-DP molecules in order to understand the pathogenesis of HBV infection and the development of hepatocellular carcinoma.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0086449</identifier><identifier>PMID: 24520320</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alleles ; Analysis ; Antigens ; Asia ; Biology ; Chronic infection ; Development and progression ; Disease Resistance - genetics ; Disease Resistance - immunology ; Ethnic Groups - genetics ; Female ; Gastroenterology ; Genes ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genetics ; Genomes ; Genotyping ; Haplotypes ; Haplotypes - genetics ; Health aspects ; Health risks ; Hepatitis ; Hepatitis B ; Hepatitis B - genetics ; Hepatitis B - immunology ; Hepatitis B virus - genetics ; Hepatocellular carcinoma ; Hepatology ; Histocompatibility antigen HLA ; HLA antigens ; HLA-DP Antigens - genetics ; Hospitals ; Humans ; Immunization ; Immunology ; Infection ; Infections ; Interferon ; Internal medicine ; Laboratories ; Leukocytes ; Liver cancer ; Liver diseases ; Male ; Medical research ; Medicine ; Meta-analysis ; Middle Aged ; Pathogenesis ; Patients ; Population genetics ; Populations ; Risk assessment ; Single-nucleotide polymorphism ; Statistical analysis ; University graduates ; Virology ; Viruses ; Young Adult</subject><ispartof>PloS one, 2014-02, Vol.9 (2), p.e86449-e86449</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Nishida et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Nishida et al 2014 Nishida et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-dba9f32ef635a24401f404e62f891e90dfe95ed9abd513ad1827c5b53b81e44c3</citedby><cites>FETCH-LOGICAL-c758t-dba9f32ef635a24401f404e62f891e90dfe95ed9abd513ad1827c5b53b81e44c3</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/PMC3919706/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3919706/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24520320$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nishida, Nao</creatorcontrib><creatorcontrib>Sawai, Hiromi</creatorcontrib><creatorcontrib>Kashiwase, Koichi</creatorcontrib><creatorcontrib>Minami, Mutsuhiko</creatorcontrib><creatorcontrib>Sugiyama, Masaya</creatorcontrib><creatorcontrib>Seto, Wai-Kay</creatorcontrib><creatorcontrib>Yuen, Man-Fung</creatorcontrib><creatorcontrib>Posuwan, Nawarat</creatorcontrib><creatorcontrib>Poovorawan, Yong</creatorcontrib><creatorcontrib>Ahn, Sang Hoon</creatorcontrib><creatorcontrib>Han, Kwang-Hyub</creatorcontrib><creatorcontrib>Matsuura, Kentaro</creatorcontrib><creatorcontrib>Tanaka, Yasuhito</creatorcontrib><creatorcontrib>Kurosaki, Masayuki</creatorcontrib><creatorcontrib>Asahina, Yasuhiro</creatorcontrib><creatorcontrib>Izumi, Namiki</creatorcontrib><creatorcontrib>Kang, Jong-Hon</creatorcontrib><creatorcontrib>Hige, Shuhei</creatorcontrib><creatorcontrib>Ide, Tatsuya</creatorcontrib><creatorcontrib>Yamamoto, Kazuhide</creatorcontrib><creatorcontrib>Sakaida, Isao</creatorcontrib><creatorcontrib>Murawaki, Yoshikazu</creatorcontrib><creatorcontrib>Itoh, Yoshito</creatorcontrib><creatorcontrib>Tamori, Akihiro</creatorcontrib><creatorcontrib>Orito, Etsuro</creatorcontrib><creatorcontrib>Hiasa, Yoichi</creatorcontrib><creatorcontrib>Honda, Masao</creatorcontrib><creatorcontrib>Kaneko, Shuichi</creatorcontrib><creatorcontrib>Mita, Eiji</creatorcontrib><creatorcontrib>Suzuki, Kazuyuki</creatorcontrib><creatorcontrib>Hino, Keisuke</creatorcontrib><creatorcontrib>Tanaka, Eiji</creatorcontrib><creatorcontrib>Mochida, Satoshi</creatorcontrib><creatorcontrib>Watanabe, Masaaki</creatorcontrib><creatorcontrib>Eguchi, Yuichiro</creatorcontrib><creatorcontrib>Masaki, Naohiko</creatorcontrib><creatorcontrib>Murata, Kazumoto</creatorcontrib><creatorcontrib>Korenaga, Masaaki</creatorcontrib><creatorcontrib>Mawatari, Yoriko</creatorcontrib><creatorcontrib>Ohashi, Jun</creatorcontrib><creatorcontrib>Kawashima, Minae</creatorcontrib><creatorcontrib>Tokunaga, Katsushi</creatorcontrib><creatorcontrib>Mizokami, Masashi</creatorcontrib><title>New susceptibility and resistance HLA-DP alleles to HBV-related diseases identified by a trans-ethnic association study in Asia</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Previous studies have revealed the association between SNPs located on human leukocyte antigen (HLA) class II genes, including HLA-DP and HLA-DQ, and chronic hepatitis B virus (HBV) infection, mainly in Asian populations. HLA-DP alleles or haplotypes associated with chronic HBV infection or disease progression have not been fully identified in Asian populations. We performed trans-ethnic association analyses of HLA-DPA1, HLA-DPB1 alleles and haplotypes with hepatitis B virus infection and disease progression among Asian populations comprising Japanese, Korean, Hong Kong, and Thai subjects. To assess the association between HLA-DP and chronic HBV infection and disease progression, we conducted high-resolution (4-digit) HLA-DPA1 and HLA-DPB1 genotyping in a total of 3,167 samples, including HBV patients, HBV-resolved individuals and healthy controls. Trans-ethnic association analyses among Asian populations identified a new risk allele HLA-DPB1*09 ∶ 01 (P = 1.36 × 10(-6); OR= 1.97; 95% CI, 1.50-2.59) and a new protective allele DPB1*02 ∶ 01 (P = 5.22 × 10(-6); OR = 0.68; 95% CI, 0.58-0.81) to chronic HBV infection, in addition to the previously reported alleles. Moreover, DPB1*02 ∶ 01 was also associated with a decreased risk of disease progression in chronic HBV patients among Asian populations (P = 1.55 × 10(-7); OR = 0.50; 95% CI, 0.39-0.65). Trans-ethnic association analyses identified Asian-specific associations of HLA-DP alleles and haplotypes with HBV infection or disease progression. The present findings will serve as a base for future functional studies of HLA-DP molecules in order to understand the pathogenesis of HBV infection and the development of hepatocellular carcinoma.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alleles</subject><subject>Analysis</subject><subject>Antigens</subject><subject>Asia</subject><subject>Biology</subject><subject>Chronic infection</subject><subject>Development and progression</subject><subject>Disease Resistance - genetics</subject><subject>Disease Resistance - immunology</subject><subject>Ethnic Groups - genetics</subject><subject>Female</subject><subject>Gastroenterology</subject><subject>Genes</subject><subject>Genetic Association Studies</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetics</subject><subject>Genomes</subject><subject>Genotyping</subject><subject>Haplotypes</subject><subject>Haplotypes - genetics</subject><subject>Health aspects</subject><subject>Health risks</subject><subject>Hepatitis</subject><subject>Hepatitis B</subject><subject>Hepatitis B - genetics</subject><subject>Hepatitis B - immunology</subject><subject>Hepatitis B virus - genetics</subject><subject>Hepatocellular carcinoma</subject><subject>Hepatology</subject><subject>Histocompatibility antigen HLA</subject><subject>HLA antigens</subject><subject>HLA-DP Antigens - genetics</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Immunization</subject><subject>Immunology</subject><subject>Infection</subject><subject>Infections</subject><subject>Interferon</subject><subject>Internal medicine</subject><subject>Laboratories</subject><subject>Leukocytes</subject><subject>Liver cancer</subject><subject>Liver diseases</subject><subject>Male</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Meta-analysis</subject><subject>Middle Aged</subject><subject>Pathogenesis</subject><subject>Patients</subject><subject>Population genetics</subject><subject>Populations</subject><subject>Risk assessment</subject><subject>Single-nucleotide polymorphism</subject><subject>Statistical analysis</subject><subject>University graduates</subject><subject>Virology</subject><subject>Viruses</subject><subject>Young 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susceptibility and resistance HLA-DP alleles to HBV-related diseases identified by a trans-ethnic association study in Asia</title><author>Nishida, Nao ; Sawai, Hiromi ; Kashiwase, Koichi ; Minami, Mutsuhiko ; Sugiyama, Masaya ; Seto, Wai-Kay ; Yuen, Man-Fung ; Posuwan, Nawarat ; Poovorawan, Yong ; Ahn, Sang Hoon ; Han, Kwang-Hyub ; Matsuura, Kentaro ; Tanaka, Yasuhito ; Kurosaki, Masayuki ; Asahina, Yasuhiro ; Izumi, Namiki ; Kang, Jong-Hon ; Hige, Shuhei ; Ide, Tatsuya ; Yamamoto, Kazuhide ; Sakaida, Isao ; Murawaki, Yoshikazu ; Itoh, Yoshito ; Tamori, Akihiro ; Orito, Etsuro ; Hiasa, Yoichi ; Honda, Masao ; Kaneko, Shuichi ; Mita, Eiji ; Suzuki, Kazuyuki ; Hino, Keisuke ; Tanaka, Eiji ; Mochida, Satoshi ; Watanabe, Masaaki ; Eguchi, Yuichiro ; Masaki, Naohiko ; Murata, Kazumoto ; Korenaga, Masaaki ; Mawatari, Yoriko ; Ohashi, Jun ; Kawashima, Minae ; Tokunaga, Katsushi ; Mizokami, Masashi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-dba9f32ef635a24401f404e62f891e90dfe95ed9abd513ad1827c5b53b81e44c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alleles</topic><topic>Analysis</topic><topic>Antigens</topic><topic>Asia</topic><topic>Biology</topic><topic>Chronic infection</topic><topic>Development and progression</topic><topic>Disease Resistance - genetics</topic><topic>Disease Resistance - immunology</topic><topic>Ethnic Groups - genetics</topic><topic>Female</topic><topic>Gastroenterology</topic><topic>Genes</topic><topic>Genetic Association Studies</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetics</topic><topic>Genomes</topic><topic>Genotyping</topic><topic>Haplotypes</topic><topic>Haplotypes - genetics</topic><topic>Health aspects</topic><topic>Health risks</topic><topic>Hepatitis</topic><topic>Hepatitis B</topic><topic>Hepatitis B - genetics</topic><topic>Hepatitis B - immunology</topic><topic>Hepatitis B virus - genetics</topic><topic>Hepatocellular carcinoma</topic><topic>Hepatology</topic><topic>Histocompatibility antigen HLA</topic><topic>HLA antigens</topic><topic>HLA-DP Antigens - genetics</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Immunization</topic><topic>Immunology</topic><topic>Infection</topic><topic>Infections</topic><topic>Interferon</topic><topic>Internal medicine</topic><topic>Laboratories</topic><topic>Leukocytes</topic><topic>Liver cancer</topic><topic>Liver diseases</topic><topic>Male</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Meta-analysis</topic><topic>Middle Aged</topic><topic>Pathogenesis</topic><topic>Patients</topic><topic>Population genetics</topic><topic>Populations</topic><topic>Risk assessment</topic><topic>Single-nucleotide polymorphism</topic><topic>Statistical analysis</topic><topic>University graduates</topic><topic>Virology</topic><topic>Viruses</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nishida, Nao</creatorcontrib><creatorcontrib>Sawai, Hiromi</creatorcontrib><creatorcontrib>Kashiwase, Koichi</creatorcontrib><creatorcontrib>Minami, Mutsuhiko</creatorcontrib><creatorcontrib>Sugiyama, Masaya</creatorcontrib><creatorcontrib>Seto, Wai-Kay</creatorcontrib><creatorcontrib>Yuen, Man-Fung</creatorcontrib><creatorcontrib>Posuwan, Nawarat</creatorcontrib><creatorcontrib>Poovorawan, Yong</creatorcontrib><creatorcontrib>Ahn, Sang Hoon</creatorcontrib><creatorcontrib>Han, Kwang-Hyub</creatorcontrib><creatorcontrib>Matsuura, Kentaro</creatorcontrib><creatorcontrib>Tanaka, Yasuhito</creatorcontrib><creatorcontrib>Kurosaki, Masayuki</creatorcontrib><creatorcontrib>Asahina, Yasuhiro</creatorcontrib><creatorcontrib>Izumi, Namiki</creatorcontrib><creatorcontrib>Kang, Jong-Hon</creatorcontrib><creatorcontrib>Hige, Shuhei</creatorcontrib><creatorcontrib>Ide, Tatsuya</creatorcontrib><creatorcontrib>Yamamoto, Kazuhide</creatorcontrib><creatorcontrib>Sakaida, Isao</creatorcontrib><creatorcontrib>Murawaki, Yoshikazu</creatorcontrib><creatorcontrib>Itoh, Yoshito</creatorcontrib><creatorcontrib>Tamori, Akihiro</creatorcontrib><creatorcontrib>Orito, Etsuro</creatorcontrib><creatorcontrib>Hiasa, Yoichi</creatorcontrib><creatorcontrib>Honda, Masao</creatorcontrib><creatorcontrib>Kaneko, Shuichi</creatorcontrib><creatorcontrib>Mita, Eiji</creatorcontrib><creatorcontrib>Suzuki, Kazuyuki</creatorcontrib><creatorcontrib>Hino, Keisuke</creatorcontrib><creatorcontrib>Tanaka, Eiji</creatorcontrib><creatorcontrib>Mochida, Satoshi</creatorcontrib><creatorcontrib>Watanabe, Masaaki</creatorcontrib><creatorcontrib>Eguchi, Yuichiro</creatorcontrib><creatorcontrib>Masaki, Naohiko</creatorcontrib><creatorcontrib>Murata, Kazumoto</creatorcontrib><creatorcontrib>Korenaga, Masaaki</creatorcontrib><creatorcontrib>Mawatari, Yoriko</creatorcontrib><creatorcontrib>Ohashi, Jun</creatorcontrib><creatorcontrib>Kawashima, Minae</creatorcontrib><creatorcontrib>Tokunaga, Katsushi</creatorcontrib><creatorcontrib>Mizokami, Masashi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology 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one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nishida, Nao</au><au>Sawai, Hiromi</au><au>Kashiwase, Koichi</au><au>Minami, Mutsuhiko</au><au>Sugiyama, Masaya</au><au>Seto, Wai-Kay</au><au>Yuen, Man-Fung</au><au>Posuwan, Nawarat</au><au>Poovorawan, Yong</au><au>Ahn, Sang Hoon</au><au>Han, Kwang-Hyub</au><au>Matsuura, Kentaro</au><au>Tanaka, Yasuhito</au><au>Kurosaki, Masayuki</au><au>Asahina, Yasuhiro</au><au>Izumi, Namiki</au><au>Kang, Jong-Hon</au><au>Hige, Shuhei</au><au>Ide, Tatsuya</au><au>Yamamoto, Kazuhide</au><au>Sakaida, Isao</au><au>Murawaki, Yoshikazu</au><au>Itoh, Yoshito</au><au>Tamori, Akihiro</au><au>Orito, Etsuro</au><au>Hiasa, Yoichi</au><au>Honda, Masao</au><au>Kaneko, Shuichi</au><au>Mita, Eiji</au><au>Suzuki, Kazuyuki</au><au>Hino, Keisuke</au><au>Tanaka, Eiji</au><au>Mochida, Satoshi</au><au>Watanabe, Masaaki</au><au>Eguchi, Yuichiro</au><au>Masaki, Naohiko</au><au>Murata, Kazumoto</au><au>Korenaga, Masaaki</au><au>Mawatari, Yoriko</au><au>Ohashi, Jun</au><au>Kawashima, Minae</au><au>Tokunaga, Katsushi</au><au>Mizokami, Masashi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>New susceptibility and resistance HLA-DP alleles to HBV-related diseases identified by a trans-ethnic association study in Asia</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-02-10</date><risdate>2014</risdate><volume>9</volume><issue>2</issue><spage>e86449</spage><epage>e86449</epage><pages>e86449-e86449</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Previous studies have revealed the association between SNPs located on human leukocyte antigen (HLA) class II genes, including HLA-DP and HLA-DQ, and chronic hepatitis B virus (HBV) infection, mainly in Asian populations. HLA-DP alleles or haplotypes associated with chronic HBV infection or disease progression have not been fully identified in Asian populations. We performed trans-ethnic association analyses of HLA-DPA1, HLA-DPB1 alleles and haplotypes with hepatitis B virus infection and disease progression among Asian populations comprising Japanese, Korean, Hong Kong, and Thai subjects. To assess the association between HLA-DP and chronic HBV infection and disease progression, we conducted high-resolution (4-digit) HLA-DPA1 and HLA-DPB1 genotyping in a total of 3,167 samples, including HBV patients, HBV-resolved individuals and healthy controls. Trans-ethnic association analyses among Asian populations identified a new risk allele HLA-DPB1*09 ∶ 01 (P = 1.36 × 10(-6); OR= 1.97; 95% CI, 1.50-2.59) and a new protective allele DPB1*02 ∶ 01 (P = 5.22 × 10(-6); OR = 0.68; 95% CI, 0.58-0.81) to chronic HBV infection, in addition to the previously reported alleles. Moreover, DPB1*02 ∶ 01 was also associated with a decreased risk of disease progression in chronic HBV patients among Asian populations (P = 1.55 × 10(-7); OR = 0.50; 95% CI, 0.39-0.65). Trans-ethnic association analyses identified Asian-specific associations of HLA-DP alleles and haplotypes with HBV infection or disease progression. The present findings will serve as a base for future functional studies of HLA-DP molecules in order to understand the pathogenesis of HBV infection and the development of hepatocellular carcinoma.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24520320</pmid><doi>10.1371/journal.pone.0086449</doi><tpages>e86449</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2014-02, Vol.9 (2), p.e86449-e86449 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1497948454 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Adolescent Adult Aged Aged, 80 and over Alleles Analysis Antigens Asia Biology Chronic infection Development and progression Disease Resistance - genetics Disease Resistance - immunology Ethnic Groups - genetics Female Gastroenterology Genes Genetic Association Studies Genetic Predisposition to Disease Genetics Genomes Genotyping Haplotypes Haplotypes - genetics Health aspects Health risks Hepatitis Hepatitis B Hepatitis B - genetics Hepatitis B - immunology Hepatitis B virus - genetics Hepatocellular carcinoma Hepatology Histocompatibility antigen HLA HLA antigens HLA-DP Antigens - genetics Hospitals Humans Immunization Immunology Infection Infections Interferon Internal medicine Laboratories Leukocytes Liver cancer Liver diseases Male Medical research Medicine Meta-analysis Middle Aged Pathogenesis Patients Population genetics Populations Risk assessment Single-nucleotide polymorphism Statistical analysis University graduates Virology Viruses Young Adult |
| title | New susceptibility and resistance HLA-DP alleles to HBV-related diseases identified by a trans-ethnic association study in Asia |
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