| Background: Initially, lower urinary tract symptoms (LUTS), aconstellation of syndrome, was used to describe benign prostatichyperplasia (BPH). However, recently studies showed that LUTS arefairly common across different age class male population, even inwomen (the current studies are only limit to men). Nowadays, LUTSwas primarily evaluated by International Prostate Symptom Score (IPSS)and divided into three groups: storage (irrigative symptoms: frequency,urgency and nocturia), voiding (obstructive symptoms: incompleteemptying, intermittency, weak stream and straining), and quality of lifeevaluation. LUTS are usually with characteristics of complex etiologies,high prevalence, difficult to cure and so on. So it constituted the maincomponent of Urology and Andrology outpatient. Increasing reportsindicate that LUTS has become a burden of patient not only physical butalso spiritual, psychological and even economic. Therefore, in order tomake better curative effect, it is very valuable to explore the etiology of LUTS.Based on the evidences which acute and chronic inflammation havebeen frequently found within prostate tissue specimens obtained fromBPH and inflammation could also be involved in overactive bladder, thenlead to LUTS, many studies have concluded that inflammation, especiallychronic inflammation, may play an important role in the progression ofLUTS. Additionally, several studies have showed C-reactive protein(CRP) which represented an acute phase of inflammation was associatedwith LUTS. On the other part, life styles (such as smoking, alcoholconsumption and physical activity) have been reported that associatedwith LUTS through changing the status of inflammation. However, mostof above studies were involved in the west population, and studies forChinese male population are relative lacking. Besides, reports haveshowed that the etiologies of LUTS may relate with heredity factor, butthere have never been studies explored its genetic correlation with agenome-wide association study.Thus, based on the Fangchenggang Area Male Health andExamination Survey (FAMHES) and the case of LUTS who come fromUrology and Andrology clinic, the objective of current studies were toexplore the role of inflammation and heredity factor in the pathogenesisof LUTS which included the following four parts: Part1: Increased High-Sensitivity C-reactive proteinPredicts a High Risk of Lower Uri nary Tract Symptomsin Chinese Male: Results from the Fangchenggang AreaMale Health and Examination SurveyObjective: Reports have shown that increased serum C-reactiveprotein (CRP) suggests a risk of lower urinary tract symptoms (LUTS) inthe west population. However, few studies have investigated the role ofCRP as regards LUTS in a Chinese male population.Methods: Data were collected from1,452men who participated inthe population-based Fangchenggang Area Male Health and ExaminationSurvey (FAMHES), which was carried out in Guangxi, China, fromSeptember2009to December2009. In the current study, serum CRP wasmeasured with a high-sensitivity method (hsCRP) and LUTS wasassessed by International Prostate Symptom Score (IPSS). Meanwhile,information about potential confounding variables (smoking,hypertension, diabetes, etc) were included.Results: We observed that statistically significant distinctionpresented in the distribution of hsCRP levels and age between LUTSgroup and non-LUTS group (P <0.001). Comparing with the lowesthsCRP tertile, men with the highest hsCRP tertile were1.72times morelikely to have overall LUTS and1.93times more likely to have irritativesymptoms. As for individual symptoms of LUTS, statistically significantcorrelations were noted between serum hsCRP levels and urgency (OR=1.74,95%CI=1.09-2.78) and nocturia (OR=1.64,95%CI=1.18-2.27),when comparing them from the1stto3rdhsCRP tertiles. Aftermultivariate adjusted, the results changed slightly and were stillsignificant.Conclusion: In a Chinese male population, we firstly confirmed a positi ve correlation of serum hsCRP with LUTS. It can be inferred thatinflammation may be involved in the processes of LUTS. Part2: High-Level Peripheral Total and Differential WhiteBlood Cells Count are Independently Associated with LowerUrinary Tract Symptoms in Chinese Male PopulationObjective: Inflammation involved in the etiology of lower urinarytract symptoms (LUTS) has been shown in majority of studies. However,the role of systemic inflammation in LUTS has not been firmlyestablished. Thus, the current study was to examine the associationbetween peripheral total and differential white blood cells count (WBCs),an important systemic inflammation marker, and LUTS in a large-scaleChinese male population.Methods: A population-based cross-sectional study of male heathamong people aged18-88years had been set up from July2011toNovember2011in Fangchenggang, Guangxi, China. In current study,4,694participants were included. Total WBCs and differential count weremeasured with an automated hematology analyzer and LUTS wereassessed by International Prostate Symptom Score (IPSS). Meanwhile,potential confounding covariates were also included. Multivariate logisticregression model was used to assess the association between total WBCsand differential count and LUTS.Results: Comparing with none/mild LUTS, the average of totalWBCs and neutrophil count was much higher in moderate/severe LUTS (P<0.001). Men who had higher total WBCs and neutrophil count levelswere more likely to report overall LUTS and obstructive symptoms, asfor individual symptoms of LUTS, primarily showed as intermittency andurgency symptoms. Besides, statistically significant associations werepresented between neutrophil count and irritative symptoms (OR=1.49,95%CI=1.08-2.05) and weak stream symptom (OR=1.93,95%CI=1.13-3.29), when comparing them from the1st to4th neutrophil countquartiles. All above associations were independent of potentialconfounding variables. Additionally, we also observed that the riskfactors of LUTS included age, hypertension, education, diabetes mellitusand alcohol drinking.Conclusions: The current study firstly showed that LUTS waspositively associated with total WBCs and differential neutrophil count,and many factors contributed to the risk of LUTS. These findings supportthe hypothesis that inflammation may be involved in the mechanism ofLUTS. Part3: Association of Alcohol Consumptionwith Lower Urinary Tract Symptoms in a Chinese MalePopulation SurveyObjectives: Several reports have investigated the associationbetween alcohol consumption and lower urinary tract symptoms (LUTS), but the results are controversial and few literatures are involved inChinese men. Thus, the current study was to evaluate the effect of thefrequency and history (times) of alcohol consumption on LUTS in a largeChinese male population.Methods: The current data were obtained from a consecutive seriesof3229men aged18-79who participated in a routine physicalexamination in Fangchenggang First People’s Hospital, Guangxi, China,which developed from September2009to December2009. During aface-to-face interview, the detailed demographic variables about alcoholconsumption and the others potential confounding factors were collected.LUTS were assessed by International Prostate Symptom Score (IPSS)and defined as total LUTS, irritative (IRR) symptoms and obstructive(OBS) symptoms, respectively. Multivariate Logistic regression analysiswas used to evaluate the risk of LUTS affected by alcohol consumption.Results: The prevalence of moderate to severe LUTS was8.3%andapparently increased with the age (P<0.001). Men who drinking1-2timesper week were less likely to have OBS symptoms (OR=0.45,95%CI=0.29-0.70) regardless of age (OR=0.52,95%CI=0.33-0.82) ormultivariate adjusted (OR=0.52,95%CI=0.33-0.83). Negativeassociation also presented between the history of alcohol consumptionand OBS symptoms among those who in the third quartile of overallsubjects (OR=0.56,95%CI=0.36-0.87), the second tertile of1-2perweek (OR=0.30,95%CI=0.15-0.61) and≤3per month (OR=0.46,95%CI=0.27-0.78) drinking and not interfered by age or others confoundingfactors when comparing with never drinkers; however, it did not show asa directly inverse association in the whole model. Conclusions: The current results implied that moderate frequency ofalcohol consumption may be protective against LUTS, and the history ofalcohol consumption did not relate to worsening or improving LUTS. Part4: A Case-Control Genome-Wide AssociationStudy for Lower Urinary Tract Symptoms in Chinese MenObjective: Many reports have indicated that the etiology of benignprostatic hyperplasia (BPH) is associated with genetic factor. Based onthe close interaction between BPH and LUTS and findings of highheritability in twins’ population of LUTS, it can be inferred which theprocessing of LUTS may be influenced by heredity, however, there havebeen few studies involved in this topic to date. Thus, the objective ofcurrent study was using the method of genome-wide association study(GWAS) to explore whether the genetic variation has influence uponLUTS or not in a Chinese male population.Methods: A case-control pattern was made in current study. Casesamples were those who had an IPSS equal or greater than8, and comefrom the out-patient department of Urology and Andrology in the303rdHospital of Chinese People’s Liberation Army, First People’s Hospital ofYulin, Guigang People’s Hospital, and First People’s Hospital of Qinzhouin Guangxi, China. Then control samples were those who had an IPSSequal to0and come from the first FAMHES (described in previous three parts). After making strict inclusion and exclusion criteria, finally1047case and1049control samples which had complete individualinformation, blood sample and the age was greater than or equal to18years were included. Aidlab DNA kit was used in DNA extraction, andthen corresponding illumina gene chips were used in genotyping.Chi-square test (χ2) was used to evaluate the distribution of age and BMI.Results: Significant statistically distinctions were presented in thedistribution of the age and BMI between case and control group(P<0.001). Comparison of expected P value and observed P value whichrepresented the association of SNPs loci and LUTS, we observed theexpansion factor (λGC) was1.04. GWAS results were presented inManhattan map, it can be seen that a SNP loci was evidently associatedwith LUTS but lacking of close linkage, so it was considered asimputation loci to be excluded. Besides, there had32SNPs locus whichsignificantly associated with LUTS (P<5×10-5), among the total the Pvalue of17SNPs locus were between10-5and10-6. In following study,we will select these17SNPs locus to validate in the second stage GWAS.Additionally, based on current study for the etiology of LUTS, two SNPswhich related closely with alcohol consumption (rs348475in ALDH1A1)and had an important effect on insuilin metabolism (rs350430in ISL1)were much more valuable to notice.Conclusions: The current study firstly showed that moderate orsevere LUTS was significantly associated with genetic factor in the firststage GWAS. It can be infered that individual genetic variation may playan important role in the processes of LUTS according to influencing themetabolism of alcohol and insulin. Certainly, the much more precise results were needed to validate in the second stage GWAS. |
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