- 學位論文
台灣含鈣尿路結石與飲食習慣及維生素D受體基因多型性之關聯性研究
The Study of the Association among Calcium Urolithiasis, Diet Habit and Vitamin D Receptor Gene Polymorphisms in Taiwan
摘要
中文摘要: 目的: 台灣地區尿路結石的盛行率約為9.6% (男性為14.5%，女性為4.3%)。由於其具有高發生率與高復發率的特性，尿路結石對於醫療與經濟上的衝擊是十分巨大！本篇研究的目的預探討國人含鈣尿路結石的危險因子，並由基因多型性(基因易感性)的角度，探討維生素D受體基因FokI的變異是否和國人尿路結石的危險性，復發性與家族史間的相關性有關。 材料與方法: 本研究設計為以醫院為基礎的病例-對照方法。從高雄醫學大學附設中和紀念醫院和高雄市立小港醫院收集診斷為含鈣成分上尿路結石的病人個案。對照組則是收集同時期保健科住院健檢之沒有尿路結石病史的病人，並作年齡配對( ± 2歲)。病例組與對照組人數比為1:1。所有病人給予受試者同意書徵得其同意，並接收泌尿科專科醫師作超音波，X光或其他影像檢查再證實。另接受問卷調查，抽血(約20ml)及收集清晨之第一泡中段尿(約20ml)以測試血清與尿液中鈣，磷，尿酸及肌酐酸的濃度。而病人維生素D受體基因多型性的檢測，是由全血萃取出DNA，以PCR方法作放大，再經由Fok I限制酶作用來分析其基因型。 結果: 本研究在民國93年7月至民國95年2月期間，在高雄醫學大學附設中和紀念醫院和高雄市立小港醫院收集診斷為含鈣成分尿路結石的病人個案共235人(161位男性與74位女性)。在同時期我们也從保健科收集了231位健康對照組(159位男性與72位女性)，納入本研究分析。在尿液中鈣離子濃度與尿酸濃度，皆為結石個案組比健康對照組來的高，且達統計學上顯著之差異(Both P<0.001)。利用多變項邏輯迴歸分析來探討結石危險因子時發現:飲用牛奶(OR: 0.48,95% CI: 0.31-0.75, P<0.001)、服用綜合維他命(OR:0.38, 95% CI: 0.20-0.75, P=0.005)、多喝水(OR:0.68, 95% CI: 0.50-0.91, P=0.01)及規律運動(OR:0.37, 95% CI: 0.20-0.75, P<0.001)為保護因子，而身體肥胖指數較高(OR:1.1, 95% CI: 1.03-1.16, P=0.001)為危險因子。雖然維生素D受體 Fok I 基因多型性在健康對照組與結石個案組間的分布並無顯著之差異(P=0.91)。但在結石個案組中發現，具有越多F allele者發生多次結石的危險性越高(P for trend=0.043)，且第一次發生結石的年齡越早(P for trend=0.037)。 結論: 維生素D受體基因FokI 多型性可能扮演著影響臨床表現的重要因素。在已發生含鈣結石的病人，具有越多F allele時越易發生多次結石，且第一次發生結石的年齡會越早。對於這些高危險之病人，需積極做飲食與生活習慣之控制並定期追蹤以預防結石的復發。預防的方式可增加飲水量，定期作運動與維持正常體位著手。
並列摘要
ABSTRACT: Purpose: The overall prevalence of upper urinary calculi in Taiwan was about 9.6%(14.5% in males and 4.3% in females). Because of high occurrence and recurrence rate of urolithiasis, burden of medical expenditure is expected to be large. This study is conducted to investigate the risk factors of calcium urolithiasis and the association with VDR gene (Fok I) polymorphism in Taiwan. Materials and Methods: The study was designed as a case-control study. Patients with calcium urolithiasis were enrolled from Kaohsiung Medical University Hospital (KMUH) and Kaohsiung Municipal Hsiao-Kang Hospital. Healthy sex and age matched ( ?b 2 years) controls were selected from patients receiving general health examinations at KMUH during the same period. All subjects were provided informed consent before enrolling into study, and received imaging study to confirm whether stone is existed. A 20 ml blood sample and first spot urine (20 ml) were obtained after getting up for biochemical analysis including calcium, phosphate, uric acid and creatinine levels. DNA was isolated from peripheral whole blood by commercial kit (Gentra System, Inc., Minneapolis, MN, USA). The VDR FokI polymorphism was detected using polymerase chain reaction-based restriction analysis. An unexcisable length of 265 bp (FF) and two fragments of 169 bp and 96 bp (ff) were obtained by digestion with restriction enzyme FokI. All patients also complete a detailed questionnaire about their demographic data, diet habits and lifestyle. Results: During June 2003 to February 2005, total 235 patients (161 males and 74 females, mean age 50.1±12.3 years, range 20-85 ) with calcium urolithiasis and 231 healthy controls (159 males and 72 females, mean age 51.7±11.1 years, range 22-85) were enrolled into this study. Urine calcium and uric acid levels were significantly higher in stone case group than normal control group (both P >0.001). In multivariate analysis for calcium urolithiasis risk after adjusting for age, sex and education levels, milk drinking (OR: 0.48,95% CI: 0.31-0.75, P<0.001),vitamins supplement (OR:0.38, 95% CI: 0.20-0.75, P=0.005),drinking more water (OR:0.68, 95% CI: 0.50-0.91, P=0.01) and regular exercise (OR:0.37, 95% CI: 0.20-0.75, P<0.001) are significant protective factors, and high BMI (OR:1.1, 95% CI: 1.03-1.16, P=0.001) is significant risk factor. Although there are no significant difference in the VDR FokI genotype distribution between stone cases and normal controls (P=0.91), but stone cases with more number of F allele have higher risk of recurrent stone episodes (P for trend=0.043) and earlier age onset (P for trend=0.037). Conclusion: The VDR FokI polymorphism may play an important role in clinical presentation of patients with calcium urolithiasis especially about stone episodes and age onset. Patients with calcium urolithiasis may be suggested to increase fluid intake, keep regular exercise, and maintain normal BMI for preventing stone recurrence.