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Single Nucleotide Polymorphisms Predict Risk Of Benign Prostatic Hyperplasia Research And Drug Efficacy

Posted on:2015-01-28Degree:DoctorType:Dissertation
Country:ChinaCandidate:X GuFull Text:PDF
GTID:1224330452966726Subject:Surgery
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Objective:Benign prostatic hyperplasia (BPH) pathogenesis is not clear. Thereare individual differences in drug efficacy which bring difficulties to thetreatment of BPH. Single nucleotide polymorphism (SNP) is a powerfultool for successful implementation of individualized treatment. Our studyanalysis the genes related with BPH pathogenesis and Drug metabolismin order to find associated SNPs which can provides the research clue andthe roadmap for BPH.Methods:From2010January to2011January, Prospectively collected clinicaldata of BPH patients in our hospital and healthy control group inShanghai city communits, including the general situation, past history,prostate index, related laboratory examination. According to the clinicaldiagnostic criteria of BPH, subjects were divided into BPH group andcontrol group; according to clinical progression criteria of BPH, BPHpatients were further divided into clinical aggressive group and non aggressive group. We use the classic case-control study design. TheMassARRAY iPLEX system was used to genotyped SNPs for all studysubjects. The Affymetrix BRLMMplat form was used to identify thegenotype of SNPs. All the statistics were analysised by genetic statistic atlast.Results:A total of426BPH patients (184for aggressive BPH and242fornon aggressive BPH) and1008healthy peoples were recruited for study.There were48SNPs selected to study. Two SNPs had been kicked outbecause they did not meet the Hardy-Weinberg Equilibrium or MAF<0.05.There were11SNPs associated with BPH risk, clinical progressionand therapeutic effect.1) There were11tagSNPs been chosen in SRD5Agenes, three of them associated with drug effect.2)16SNPs had beenproven to associate with prostate volume in Chinese. We found3SNPsassociated with BPH risk,3SNPs associated with BPH progression and3SNPs associated with drug effect.3) In9SNPs related with insulinresistance genes, we found1SNPs associated with BPH risk and2SNPsassociated with drug effect.4) There were12SNPs associated with BPHin non Han people, but we only found one of them associated with drugeffect.Conclusions:1)The SNPs of SRD5A1å'ŒSRD5A2genes can predict drug effect of BPH.2) Prostate cancer susceptibility gene mutations are associated withBPH and can predict BPH risk and drug effect.3) SNPs related with insulin resistance are proven to associate withBPH risk and drug effect.4) There are racial differences between of gene polymorphism andBPH.
Keywords/Search Tags:Benign prostatic hyperplasia, Single nucleotidepolymorphism, Drug effect, Risk
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