Objective The leptin receptor,encoded by the LEPR gene,is involved in tumorigenesis.A potential functional variant of LEPR,rs1137101(Gln223Arg),has been extensively investigated for its contribution to the risk of dig...Objective The leptin receptor,encoded by the LEPR gene,is involved in tumorigenesis.A potential functional variant of LEPR,rs1137101(Gln223Arg),has been extensively investigated for its contribution to the risk of digestive system(DS)cancers,but results remain conflicting rather than conclusive.Here,we performed a case–control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk.Methods A total of 1,727 patients with cancer(gastric/liver/colorectal:460/480/787)and 800 healthy controls were recruited.Genotyping of rs1137101 was conducted using a polymerase chain reactionrestriction fragment length polymorphism(PCR-RFLP)assay and confirmed using Sanger sequencing.Twenty-four eligible studies were included in the meta-analysis.Results After Bonferroni correction,the case–control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population.The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS,gastric,and liver cancer in the Chinese population.Conclusion The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers(especially liver and gastric cancer)in the Chinese population.展开更多
瘦素和瘦素受体参与了乳腺癌的发生发展过程。在瘦素受体基因（LEPR）6号外显子上第223个密码子A到G的转变可以导致谷氨酸到精氨酸的替换（Gln223Arg）。许多已发表的病例对照研究评价了LEPRGln223Arg多态性与乳腺癌的关系。然而，却未...瘦素和瘦素受体参与了乳腺癌的发生发展过程。在瘦素受体基因（LEPR）6号外显子上第223个密码子A到G的转变可以导致谷氨酸到精氨酸的替换（Gln223Arg）。许多已发表的病例对照研究评价了LEPRGln223Arg多态性与乳腺癌的关系。然而，却未得出一致的结论。本篇meta分析囊括了8篇文献来评价LEPRGln223Arg多态性与乳腺癌的联系。用总体合并OR值作为研究共显性模型、隐性模型、显性模型的指标。结果显示总体研究中隐性模型（OR=1．32，95％CI：1．03～1．69）和Arg/Gln vs Gin／Gin基因型（OR=1．16，95％CI：1．01～1．34）显著提高了乳腺癌的危险性。种族分层分析中发现，非洲人群的以下几个基因型会提高患乳腺癌的危险性：Arg/Arg vs 8Gln/Gln（OR=1．86，95％CI：1．28-2．71），Arg／Gln vs GIn/Gln（OR=1．48，95％CI：1．10—1．99），显性模型（OR=1．60，95％CI：1．21～2．11）和隐性模型（OR=1．48，95％cI：1．07～2．05）；亚洲人群中，Arg／ArgvsGin／Gin基因型（OR=6．79，95％CI：3．42～13．47）和显性模型（OR=2．03，95％CI：1．42～2．90）提高了患乳腺癌的危险性。在欧洲人群中任何基因模型都没有发现能显著提高乳腺癌的危险性。总而言之，LEPR223Arg是乳腺癌发展的低风险因素，特别是在非洲女性中。展开更多
Leptin receptor(LEPR)plays a vital role in obesity in humans and animals.The objective of this study is to assess LEPR functional variants for chicken adipose deposition by integration of association and in-silico ana...Leptin receptor(LEPR)plays a vital role in obesity in humans and animals.The objective of this study is to assess LEPR functional variants for chicken adipose deposition by integration of association and in-silico analysis using a unique chicken population,the Northeast Agricultural University broiler lines divergently selected for abdominal fat content(NEAUHLF).Five online bioinformatics tools were used to predict the functionality of the single nucleotide polymorphisms(SNPs)in coding region.Further,the possible structure–function relationship of high confidence SNPs was determined by bioinformatics analyses,including the conservation and stability analysis based on amino acid residues,prediction of protein ligand-binding sites,and the superposition of protein tertiary structure.Meanwhile,we analyzed the association between abdominal fat traits and 20 polymorphisms of chicken LEPR gene.The integrated results showed that rs731962924(N867I)and rs13684622(C1002R)could lead to striking changes in the structure and function of proteins,of which rs13684622(C1002R)was significantly associated with abdominal fat weight(AFW,P=0.0413)and abdominal fat percentage(AFP,P=0.0260)in chickens.Therefore,we are of the opinion that rs13684622(C1002R)may be an essential functional SNP affecting chicken abdominal fat deposition,and potentially applied to improvement of broiler abdominal fat in molecular marker-assisted selection(MAS)program.Additionally,the coupling of association with computer electronic predictive analysis provides a new avenue to identify important molecular markers for breeders.展开更多
基金supported by the Fundamental Research Funds for the Central Universities(WUT:2020IB029)。
文摘Objective The leptin receptor,encoded by the LEPR gene,is involved in tumorigenesis.A potential functional variant of LEPR,rs1137101(Gln223Arg),has been extensively investigated for its contribution to the risk of digestive system(DS)cancers,but results remain conflicting rather than conclusive.Here,we performed a case–control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk.Methods A total of 1,727 patients with cancer(gastric/liver/colorectal:460/480/787)and 800 healthy controls were recruited.Genotyping of rs1137101 was conducted using a polymerase chain reactionrestriction fragment length polymorphism(PCR-RFLP)assay and confirmed using Sanger sequencing.Twenty-four eligible studies were included in the meta-analysis.Results After Bonferroni correction,the case–control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population.The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS,gastric,and liver cancer in the Chinese population.Conclusion The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers(especially liver and gastric cancer)in the Chinese population.
文摘瘦素和瘦素受体参与了乳腺癌的发生发展过程。在瘦素受体基因（LEPR）6号外显子上第223个密码子A到G的转变可以导致谷氨酸到精氨酸的替换（Gln223Arg）。许多已发表的病例对照研究评价了LEPRGln223Arg多态性与乳腺癌的关系。然而，却未得出一致的结论。本篇meta分析囊括了8篇文献来评价LEPRGln223Arg多态性与乳腺癌的联系。用总体合并OR值作为研究共显性模型、隐性模型、显性模型的指标。结果显示总体研究中隐性模型（OR=1．32，95％CI：1．03～1．69）和Arg/Gln vs Gin／Gin基因型（OR=1．16，95％CI：1．01～1．34）显著提高了乳腺癌的危险性。种族分层分析中发现，非洲人群的以下几个基因型会提高患乳腺癌的危险性：Arg/Arg vs 8Gln/Gln（OR=1．86，95％CI：1．28-2．71），Arg／Gln vs GIn/Gln（OR=1．48，95％CI：1．10—1．99），显性模型（OR=1．60，95％CI：1．21～2．11）和隐性模型（OR=1．48，95％cI：1．07～2．05）；亚洲人群中，Arg／ArgvsGin／Gin基因型（OR=6．79，95％CI：3．42～13．47）和显性模型（OR=2．03，95％CI：1．42～2．90）提高了患乳腺癌的危险性。在欧洲人群中任何基因模型都没有发现能显著提高乳腺癌的危险性。总而言之，LEPR223Arg是乳腺癌发展的低风险因素，特别是在非洲女性中。
基金This work was supported by the National Natural Science Foundation of China(31572394)the China Agriculture Research System of MOF and MARA(CARS-41)the White Feather Broiler Breeding Joint Project of the Ministry of Agriculture and Rural Affairs of China(19190526).
文摘Leptin receptor(LEPR)plays a vital role in obesity in humans and animals.The objective of this study is to assess LEPR functional variants for chicken adipose deposition by integration of association and in-silico analysis using a unique chicken population,the Northeast Agricultural University broiler lines divergently selected for abdominal fat content(NEAUHLF).Five online bioinformatics tools were used to predict the functionality of the single nucleotide polymorphisms(SNPs)in coding region.Further,the possible structure–function relationship of high confidence SNPs was determined by bioinformatics analyses,including the conservation and stability analysis based on amino acid residues,prediction of protein ligand-binding sites,and the superposition of protein tertiary structure.Meanwhile,we analyzed the association between abdominal fat traits and 20 polymorphisms of chicken LEPR gene.The integrated results showed that rs731962924(N867I)and rs13684622(C1002R)could lead to striking changes in the structure and function of proteins,of which rs13684622(C1002R)was significantly associated with abdominal fat weight(AFW,P=0.0413)and abdominal fat percentage(AFP,P=0.0260)in chickens.Therefore,we are of the opinion that rs13684622(C1002R)may be an essential functional SNP affecting chicken abdominal fat deposition,and potentially applied to improvement of broiler abdominal fat in molecular marker-assisted selection(MAS)program.Additionally,the coupling of association with computer electronic predictive analysis provides a new avenue to identify important molecular markers for breeders.
