尿路結石是複雜和遺傳的疾病，其形成的過程被稱為生物礦化，真正的機轉雖然尚未清楚，但是生物分子可能參與其中，我們研究的目標是以生化學和分子遺傳學的方法來探討尿路結石形成的機制。
腎調鈣素、Tamm-Horsfall蛋白和白蛋白對草算鈣結晶形成的作用是以成核、晶體成長和晶體聚集的步驟分別測試的，Tamm-Horsfall蛋白和白蛋白對晶體成核是以促進的作用，二者在晶體成長和聚集均呈抑制作用，腎調鈣素能抑制晶體成長，但在加入維生素C和銅離子作用後斷成兩個胜□而失去作用。

由於促進成核會使後續晶體成長和聚集所需的濃度減少因此無法形成大的晶體，所以Tamm-Horsfall蛋白和白蛋白對草酸鈣晶體的整體作用是抑制因子，腎調鈣素也是抑制因子，維生素C和銅離子對草酸鈣晶體的作用需要進一步臨床上的研究來驗證。

核酸多形性是用來尋找複雜疾病關聯基因的方法，但是目前很少有此類相關的研究，我們以病例-控制的方法來比較正常人和結石病人基因上標記位置對偶基因出現的頻率。維生素D受體基因開始碼和第八插入序列、降血鈣素受體、p21基因、破骨素基因、白血球介素1β基因開始碼和第五插入序列、白血球介素1受體拮抗基因第二插入序列雄性素受體基因和雌性素受體基因等多形性是選用測試與尿路結石關聯性的基因。

以聚合□鏈鎖反應為基礎的限制□分析法是用來檢測的方法，結果顯示，維生素D受體基因開始碼、降血鈣素受體、p21基因、白血球介素1受體拮抗基因第二插入序列和雄性素受體基因（只限男性病人）等多形性與尿路結石有相關聯，其風險對比值分別為1.672, 5.634, 1.39, 6.041,和0.328（男病患低風險值）；而維生素D受體基因第八插入序列、破骨素基因、白血球介素1β基因開始碼和第五插入序列、雄性素受體基因和雌性素受體基因（女性病患）則無統計學上的差異。

雖然正相關並不代表此基因一定會在臨床上造成疾病，但是它可以運用於與危險因子交互作用的探討，計量基因與環境因子的交互作用可以算出那些因子可能有結石的高危險性，以達到預防的目的。本研究可以幫助我們了解那些基因適合作為與結石病的關聯性探討，也了解腎調鈣素、Tamm-Horsfall蛋白和白蛋白是草酸鈣晶體形成的抑制因子，因此以生化學和分子遺傳學的方法可以協助研究尿路結石的生物礦化過程。

Urolithiasis is a complex genetic traits disease that the formation is regarded as a process of biomineralization. The exact mechanism of the stone formation is still unclear. However, biomolecules are proposed to play a role in the biomineralization. In this study, we aimed to investigate the mechanism of stone formation through biochemistry and molecular genetics.
Effects of nephrocalcin, Tamm-Horsfall protein, and albumin on calcium oxalate crystallization were tested through crystal nucleation, crystal growth, and crystal aggregation which were determined by spectrophotometry. Albumin and Tamm-Horsfall proteins exerted a promoting effect of nucleation in this study. Inhibitory effects of these proteins on crystal growth and crystal aggregation were found in this study. Nephrocalcin showed an inhibitory effect on the crystal growth but lost its effect when nephrocalcin was fragmented into two short peptides by the interaction with added ascorbic acid and copper ions in the solution.

Being able to promote the nucleation of calcium oxalate crystal and then reduce the concentration of calcium and oxalate ions, Tamm-Horsfall protein and albumin showed an overall effect of inhibition in the calcium oxalate crystallization. Nephrocalcin is also an inhibitor in the crystallization of calcium oxalate. The influence of ascorbic acid and copper ions in calcium oxalate stone formation should be further studied clinically.

Genetic polymorphisms were used in the identification of associated genes with complex disease. To our knowledge, fewer studies were done on the urolithiasis. Case-control studies comparing the allele frequencies of candidate genes between affected individuals and unaffected individuals were performed. Vitamin D receptor gene (start codon and intron 8), calcitonin receptor gene (the 1377th nucleotide), p21 gene (codon 31), osteocalcin gene, interleukin 1β gene (start codon and intorn 5), interleukin 1 receptor antagonist gene (intron 2), androgen receptor gene (CAG repeats), and estrogen receptor gene (TA repeats) polymorphisms were tested for the association with urolithiasis.

Polymerase chain reaction based restriction analyses were used for the association study. The results indicated that vitamin D receptor gene, calcitonin receptor gene, p21 gene, interleukin 1 receptor antagonist gene, and androgen receptor gene (only for male patients) polymorphisms are associated with urolithiasis. The odds ratios for the risk of disease were 1.672, 5.634, 1.39, 6.041, and 0.328 (for low risk), respectively. No statistically significant difference were found in vitamin D receptor gene intron 8, osteocalcin, interleukin 1β gene start codon and intorn 5, and androgen receptor gene (for female patients) polymorphisms.

Although positive association does not necessarily imply carrying the genes will develop clinical disease, it worth to be further studied for the interaction of genes and some risk factors. Documenting gene-environmental interactions may identify groups at highest risk for the stone formation. In conclusion, it is helpful to understand the candidate genes through studies of genetic polymorphisms. Studies effects of proteins on crystallizations are also helpful to understand the inhibitor roles of nephrocalcin, Tamm-Horsfall protein and albumin. The approach through biochemistry and molecular genetics can get further information on the biomineralized processes of urolithiasis.

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