Genetic polymorphisms of Ca2+ transport proteins and molecular chaperones in mitochondria-associated endoplasmic reticulum membrane and non-alcoholic fatty liver disease
BackgroundNon-alcoholic fatty liver disease (NAFLD) is recognized to be closely associated with endoplasmic reticulum stress and mitochondrial dysfunction, while previous studies have emphasized the important role of calcium homeostasis from the mitochondria-associated endoplasmic reticulum membrane...
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.1056283/full |
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| author | Zongzhe Tang Yajie Ding Ru Zhang Mengting Zhang Qing Guan Liuxin Zhang Hongliang Wang Yue Chen Rong Jiang Wei Zhang Jie Wang |
| author_facet | Zongzhe Tang Yajie Ding Ru Zhang Mengting Zhang Qing Guan Liuxin Zhang Hongliang Wang Yue Chen Rong Jiang Wei Zhang Jie Wang |
| author_sort | Zongzhe Tang |
| collection | DOAJ |
| description | BackgroundNon-alcoholic fatty liver disease (NAFLD) is recognized to be closely associated with endoplasmic reticulum stress and mitochondrial dysfunction, while previous studies have emphasized the important role of calcium homeostasis from the mitochondria-associated endoplasmic reticulum membrane (MAM) in the endoplasmic reticulum and mitochondria. This article will assess the association between genetic polymorphisms of Ca2+ transport proteins and molecular chaperones in MAM and NAFLD risk.MethodsA case-control study was conducted in a community of Nanjing, China during April to December 2020. 2701 subjects were enrolled and genotyped for 6 genetic variants in HSPA5 and ITPR2 genes. Logistic regression analysis was used to assess impact of these variants on NAFLD risk.ResultsAfter adjusting for age, gender, total cholesterol and glucose, we identified that HSPA5 rs12009 variant genotypes (recessive model: OR= 0.801, 95% CI= 0.652-0.986, P= 0.036), rs430397 variant genotypes (recessive model: OR= 0.546, 95% CI= 0.314-0.950, P= 0.032), and ITPR2 rs11048570 variant genotypes (recessive model: OR= 0.673, 95% CI= 0.453-0.999, P= 0.049) were associated with a reduced risk of NAFLD. Multivariate stepwise regression analysis indicated that gender, glucose, body mass index, triglycerides and favorable alleles were independent influencers of NAFLD (all P< 0.05). The area under the receiver operating characteristic curve was 0.764 (95% CI= 0.745-0.783, P< 0.001).ConclusionThe variant genotypes of Ca2+ transport-associated genes HSPA5 (rs12009 and rs430397) and ITPR2 (rs11048570) might contribute to the reduction of the NAFLD risk in Chinese Han population, which can provide new insight into NAFLD pathogenesis. |
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| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-11T01:01:00Z |
| publishDate | 2023-01-01 |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-8801bb770a94485da0fad4af55cf89692023-01-04T16:23:23ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-01-011310.3389/fendo.2022.10562831056283Genetic polymorphisms of Ca2+ transport proteins and molecular chaperones in mitochondria-associated endoplasmic reticulum membrane and non-alcoholic fatty liver diseaseZongzhe Tang0Yajie Ding1Ru Zhang2Mengting Zhang3Qing Guan4Liuxin Zhang5Hongliang Wang6Yue Chen7Rong Jiang8Wei Zhang9Jie Wang10Department of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, ChinaDepartment of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, ChinaDepartment of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, ChinaDepartment of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, ChinaDepartment of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, ChinaDepartment of Neurosurgery, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of General Practice, Ninghai Road Community Health Service Center, Nanjing, ChinaDepartment of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, ChinaDepartment of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, ChinaDepartment of Epidemiology, Shanghai Cancer Institute, Shanghai, ChinaDepartment of Fundamental and Community Nursing, School of Nursing, Nanjing Medical University, Nanjing, ChinaBackgroundNon-alcoholic fatty liver disease (NAFLD) is recognized to be closely associated with endoplasmic reticulum stress and mitochondrial dysfunction, while previous studies have emphasized the important role of calcium homeostasis from the mitochondria-associated endoplasmic reticulum membrane (MAM) in the endoplasmic reticulum and mitochondria. This article will assess the association between genetic polymorphisms of Ca2+ transport proteins and molecular chaperones in MAM and NAFLD risk.MethodsA case-control study was conducted in a community of Nanjing, China during April to December 2020. 2701 subjects were enrolled and genotyped for 6 genetic variants in HSPA5 and ITPR2 genes. Logistic regression analysis was used to assess impact of these variants on NAFLD risk.ResultsAfter adjusting for age, gender, total cholesterol and glucose, we identified that HSPA5 rs12009 variant genotypes (recessive model: OR= 0.801, 95% CI= 0.652-0.986, P= 0.036), rs430397 variant genotypes (recessive model: OR= 0.546, 95% CI= 0.314-0.950, P= 0.032), and ITPR2 rs11048570 variant genotypes (recessive model: OR= 0.673, 95% CI= 0.453-0.999, P= 0.049) were associated with a reduced risk of NAFLD. Multivariate stepwise regression analysis indicated that gender, glucose, body mass index, triglycerides and favorable alleles were independent influencers of NAFLD (all P< 0.05). The area under the receiver operating characteristic curve was 0.764 (95% CI= 0.745-0.783, P< 0.001).ConclusionThe variant genotypes of Ca2+ transport-associated genes HSPA5 (rs12009 and rs430397) and ITPR2 (rs11048570) might contribute to the reduction of the NAFLD risk in Chinese Han population, which can provide new insight into NAFLD pathogenesis.https://www.frontiersin.org/articles/10.3389/fendo.2022.1056283/fullnon-alcoholic fatty liver disease (NAFLD)heat shock 70-kDa protein 5 (HSPA5)inositol 1,4,5-trisphosphate receptor type 2 (ITPR2)genetic polymorphismcalcium homeostasis |
| spellingShingle | Zongzhe Tang Yajie Ding Ru Zhang Mengting Zhang Qing Guan Liuxin Zhang Hongliang Wang Yue Chen Rong Jiang Wei Zhang Jie Wang Genetic polymorphisms of Ca2+ transport proteins and molecular chaperones in mitochondria-associated endoplasmic reticulum membrane and non-alcoholic fatty liver disease Frontiers in Endocrinology non-alcoholic fatty liver disease (NAFLD) heat shock 70-kDa protein 5 (HSPA5) inositol 1,4,5-trisphosphate receptor type 2 (ITPR2) genetic polymorphism calcium homeostasis |
| title | Genetic polymorphisms of Ca2+ transport proteins and molecular chaperones in mitochondria-associated endoplasmic reticulum membrane and non-alcoholic fatty liver disease |
| title_full | Genetic polymorphisms of Ca2+ transport proteins and molecular chaperones in mitochondria-associated endoplasmic reticulum membrane and non-alcoholic fatty liver disease |
| title_fullStr | Genetic polymorphisms of Ca2+ transport proteins and molecular chaperones in mitochondria-associated endoplasmic reticulum membrane and non-alcoholic fatty liver disease |
| title_full_unstemmed | Genetic polymorphisms of Ca2+ transport proteins and molecular chaperones in mitochondria-associated endoplasmic reticulum membrane and non-alcoholic fatty liver disease |
| title_short | Genetic polymorphisms of Ca2+ transport proteins and molecular chaperones in mitochondria-associated endoplasmic reticulum membrane and non-alcoholic fatty liver disease |
| title_sort | genetic polymorphisms of ca2 transport proteins and molecular chaperones in mitochondria associated endoplasmic reticulum membrane and non alcoholic fatty liver disease |
| topic | non-alcoholic fatty liver disease (NAFLD) heat shock 70-kDa protein 5 (HSPA5) inositol 1,4,5-trisphosphate receptor type 2 (ITPR2) genetic polymorphism calcium homeostasis |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.1056283/full |
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