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
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.
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.