Interaction Between AGTR1 and PPARγ Gene Polymorphisms on the Risk of Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is an important public health issue worldwide. Several recent studies have reported that peroxisome proliferator-activated receptor-γ (PPARγ) and angiotensin II type 1 receptor (AGTR1) variants are associated with NAFLD occurrence, but the results have been i...

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Veröffentlicht in:Genetic testing and molecular biomarkers 2019-03, Vol.23 (3), p.166-175
Hauptverfasser: Zhu, Peifu, Lu, Honghong, Jing, Yang, Zhou, Hui, Ding, Yi, Wang, Jie, Guo, Daoxia, Guo, Zhirong, Dong, Chen
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container_end_page 175
container_issue 3
container_start_page 166
container_title Genetic testing and molecular biomarkers
container_volume 23
creator Zhu, Peifu
Lu, Honghong
Jing, Yang
Zhou, Hui
Ding, Yi
Wang, Jie
Guo, Daoxia
Guo, Zhirong
Dong, Chen
description Nonalcoholic fatty liver disease (NAFLD) is an important public health issue worldwide. Several recent studies have reported that peroxisome proliferator-activated receptor-γ (PPARγ) and angiotensin II type 1 receptor (AGTR1) variants are associated with NAFLD occurrence, but the results have been inconsistent. The aim of this study was to analyze the interactions between PPARγ and AGTR1 polymorphisms and their associations with NAFLD in Chinese adults. Seven single nucleotide polymorphisms (SNPs) of the PPARγ gene and 5 SNPs of the AGTR1 gene were selected and genotyped in 1591 unrelated Chinese adults. The SNPAssoc package of R was used to examine the relationships between the selected SNPs and NAFLD. After adjusting the covariance, the results from the overdominant model showed that participants carrying the T/C genotype of rs2638360 in AGTR1 have a decreased risk of NAFLD compared with those with T/T-C/C genotypes (odds ratio: 0.70, 95% confidence interval: 0.49-1.00). However, our results showed that none of the selected PPARγ variants were significantly associated with the risk of NAFLD after applying a false discovery rate correction. Among the 12 selected SNPs from PPARγ and AGTR1, model-based multifactor dimensionality reduction (MB-MDR) analyses for gene-gene interactions revealed that all the models were significantly associated with the increased risk of NAFLD (p 
doi_str_mv 10.1089/gtmb.2018.0203
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Several recent studies have reported that peroxisome proliferator-activated receptor-γ (PPARγ) and angiotensin II type 1 receptor (AGTR1) variants are associated with NAFLD occurrence, but the results have been inconsistent. The aim of this study was to analyze the interactions between PPARγ and AGTR1 polymorphisms and their associations with NAFLD in Chinese adults. Seven single nucleotide polymorphisms (SNPs) of the PPARγ gene and 5 SNPs of the AGTR1 gene were selected and genotyped in 1591 unrelated Chinese adults. The SNPAssoc package of R was used to examine the relationships between the selected SNPs and NAFLD. After adjusting the covariance, the results from the overdominant model showed that participants carrying the T/C genotype of rs2638360 in AGTR1 have a decreased risk of NAFLD compared with those with T/T-C/C genotypes (odds ratio: 0.70, 95% confidence interval: 0.49-1.00). However, our results showed that none of the selected PPARγ variants were significantly associated with the risk of NAFLD after applying a false discovery rate correction. Among the 12 selected SNPs from PPARγ and AGTR1, model-based multifactor dimensionality reduction (MB-MDR) analyses for gene-gene interactions revealed that all the models were significantly associated with the increased risk of NAFLD (p &lt; 0.05) except the 2-, 10-, 11-, and 12-locus models. Further, among the 10 SNPs negatively associated with NAFLD, the four-locus model (rs13431696 and rs3856806 in PPARγ, and rs5182, rs1492100 in ATGR1) and the five-locus model (rs9817428, rs1175543, rs13433696, and rs2920502 in PPARγ, and rs1492100 in ATGR1) were closely related with NAFLD susceptibility (p = 0.019 and p = 0.048, respectively). Our present study suggests that interactions among multiple AGTR1 and PPARγ polymorphisms are associated with the risk of NAFLD in the Chinese population.</description><identifier>ISSN: 1945-0265</identifier><identifier>EISSN: 1945-0257</identifier><identifier>DOI: 10.1089/gtmb.2018.0203</identifier><identifier>PMID: 30793973</identifier><language>eng</language><publisher>United States</publisher><ispartof>Genetic testing and molecular biomarkers, 2019-03, Vol.23 (3), p.166-175</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c295t-317bfe5a6fb484d2c123b7a3a4fdbcf2ffceac9b986dcf441b9bc05e3f8d59fd3</citedby><cites>FETCH-LOGICAL-c295t-317bfe5a6fb484d2c123b7a3a4fdbcf2ffceac9b986dcf441b9bc05e3f8d59fd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30793973$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhu, Peifu</creatorcontrib><creatorcontrib>Lu, Honghong</creatorcontrib><creatorcontrib>Jing, Yang</creatorcontrib><creatorcontrib>Zhou, Hui</creatorcontrib><creatorcontrib>Ding, Yi</creatorcontrib><creatorcontrib>Wang, Jie</creatorcontrib><creatorcontrib>Guo, Daoxia</creatorcontrib><creatorcontrib>Guo, Zhirong</creatorcontrib><creatorcontrib>Dong, Chen</creatorcontrib><title>Interaction Between AGTR1 and PPARγ Gene Polymorphisms on the Risk of Nonalcoholic Fatty Liver Disease</title><title>Genetic testing and molecular biomarkers</title><addtitle>Genet Test Mol Biomarkers</addtitle><description>Nonalcoholic fatty liver disease (NAFLD) is an important public health issue worldwide. Several recent studies have reported that peroxisome proliferator-activated receptor-γ (PPARγ) and angiotensin II type 1 receptor (AGTR1) variants are associated with NAFLD occurrence, but the results have been inconsistent. The aim of this study was to analyze the interactions between PPARγ and AGTR1 polymorphisms and their associations with NAFLD in Chinese adults. Seven single nucleotide polymorphisms (SNPs) of the PPARγ gene and 5 SNPs of the AGTR1 gene were selected and genotyped in 1591 unrelated Chinese adults. The SNPAssoc package of R was used to examine the relationships between the selected SNPs and NAFLD. After adjusting the covariance, the results from the overdominant model showed that participants carrying the T/C genotype of rs2638360 in AGTR1 have a decreased risk of NAFLD compared with those with T/T-C/C genotypes (odds ratio: 0.70, 95% confidence interval: 0.49-1.00). However, our results showed that none of the selected PPARγ variants were significantly associated with the risk of NAFLD after applying a false discovery rate correction. Among the 12 selected SNPs from PPARγ and AGTR1, model-based multifactor dimensionality reduction (MB-MDR) analyses for gene-gene interactions revealed that all the models were significantly associated with the increased risk of NAFLD (p &lt; 0.05) except the 2-, 10-, 11-, and 12-locus models. Further, among the 10 SNPs negatively associated with NAFLD, the four-locus model (rs13431696 and rs3856806 in PPARγ, and rs5182, rs1492100 in ATGR1) and the five-locus model (rs9817428, rs1175543, rs13433696, and rs2920502 in PPARγ, and rs1492100 in ATGR1) were closely related with NAFLD susceptibility (p = 0.019 and p = 0.048, respectively). 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Several recent studies have reported that peroxisome proliferator-activated receptor-γ (PPARγ) and angiotensin II type 1 receptor (AGTR1) variants are associated with NAFLD occurrence, but the results have been inconsistent. The aim of this study was to analyze the interactions between PPARγ and AGTR1 polymorphisms and their associations with NAFLD in Chinese adults. Seven single nucleotide polymorphisms (SNPs) of the PPARγ gene and 5 SNPs of the AGTR1 gene were selected and genotyped in 1591 unrelated Chinese adults. The SNPAssoc package of R was used to examine the relationships between the selected SNPs and NAFLD. After adjusting the covariance, the results from the overdominant model showed that participants carrying the T/C genotype of rs2638360 in AGTR1 have a decreased risk of NAFLD compared with those with T/T-C/C genotypes (odds ratio: 0.70, 95% confidence interval: 0.49-1.00). However, our results showed that none of the selected PPARγ variants were significantly associated with the risk of NAFLD after applying a false discovery rate correction. Among the 12 selected SNPs from PPARγ and AGTR1, model-based multifactor dimensionality reduction (MB-MDR) analyses for gene-gene interactions revealed that all the models were significantly associated with the increased risk of NAFLD (p &lt; 0.05) except the 2-, 10-, 11-, and 12-locus models. Further, among the 10 SNPs negatively associated with NAFLD, the four-locus model (rs13431696 and rs3856806 in PPARγ, and rs5182, rs1492100 in ATGR1) and the five-locus model (rs9817428, rs1175543, rs13433696, and rs2920502 in PPARγ, and rs1492100 in ATGR1) were closely related with NAFLD susceptibility (p = 0.019 and p = 0.048, respectively). Our present study suggests that interactions among multiple AGTR1 and PPARγ polymorphisms are associated with the risk of NAFLD in the Chinese population.</abstract><cop>United States</cop><pmid>30793973</pmid><doi>10.1089/gtmb.2018.0203</doi><tpages>10</tpages></addata></record>
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