Genetic Variation at Selected SNPs in the Leptin Gene and Association of Alleles with Markers of Kidney Disease in a Xhosa Population of South Africa 英文参考文献.docVIP

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Genetic Variation at Selected SNPs in the Leptin Gene and Association of Alleles with Markers of Kidney Disease in a Xhosa Population of South Africa 英文参考文献.doc

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Genetic Variation at Selected SNPs in the Leptin Gene and Association of Alleles with Markers of Kidney Disease in a Xhosa Population of South Africa 英文参考文献

GeneticVariationatSelectedSNPsintheLeptinGene andAssociationofAlleleswithMarkersofKidney DiseaseinaXhosaPopulationofSouthAfrica IkechiG.Okpechi1*,BrianL.Rayner1,LizevanderMerwe2,BonganiM.Mayosi1,AdebowaleAdeyemo3, NickiTiffin4,RajkumarRamesar4 1DepartmentofMedicine,GrooteSchuurHospitalandUniversityofCapeTown,CapeTown,SouthAfrica,2DepartmentofStatistics,UniversityoftheWesternCape, Cape Town, South Africa, 3Centre for Research on Genomics and Global Health, National Human Genome Research Institute, Bethesda, Maryland, United States of America,4DivisionofHumanGenetics,InstituteforInfectiousDiseasesandMolecularMedicine,UniversityofCapeTown,CapeTown,SouthAfrica Abstract Background: Chronic kidney disease (CKD) is a significant public health problem that leads to end-stage renal disease (ESRD)withasmanyas2millionpeoplepredictedtoneedtherapyworldwideby2010.ObesityisariskfactorforCKDand leptin, the obesity hormone, correlates with body fat mass and markers of renal function. A number of clinical and experimentalstudieshavesuggestedalinkbetweenserumleptinandkidneydisease.Wehypothesisedthatvariantsinthe leptingene(LEP)maybeassociatedwithmarkersofCKDinindigenousblackAfricans. Methodology/PrincipalFindings:BlackSouthAfricansofXhosa(distinctculturalBantu-speakingpopulation)descentwere recruited for the study and four common polymorphisms of the LEP (rs7799039, rs791620, rs2167270 and STS-U43653 [ENSSNP5824596]) were analysed for genotype and haplotype association with urine albumin-to-creatinine ratio (UACR), estimatedglomerularfiltrationrate(eGFR),Serumcreatinine(Scr)andserumleptinlevel.Inoneofthefoursinglenucleotide polymorphisms(SNPs)weexamined,anassociationwiththerenalphenotypeswasobserved.Hypertensivesubjectswith theTallele(CTgenotype)oftheENSSNP5824596SNPhadasignificantlyhighereGFR(p=0.0141),andsignificantlylower Scr(p=0.0137).Thiswasconfirmedbyhaplotypeanalysis.Also,thehaplotypeGAAChadamodesteffectonurinealbumin- to-creatinineratioinnormotensivesubjects(p=0.0482). Concl