探討台灣族群鈣離子通道基因多型性在慢性腎臟疾病發展和紅血球生成素阻抗之角色

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Title:	探討台灣族群鈣離子通道基因多型性在慢性腎臟疾病發展和紅血球生成素阻抗之角色 The Association Study between Genetics Polymorphism of Calcium Channel Transporters and the Progression of Chronic Kidney Disease and EPO Resistance in Taiwanese Population
Authors:	呂蕙均 Lu, Hui-Chen
Contributors:	張偉嶠
Keywords:	慢性腎臟疾病;末期腎臟疾病;基因多型性;慢性腎臟疾病發展;紅血球生成素阻抗性;微陣列 chronic kidney disease;end-stage renal diseases;polymorphism;CKD progression;EPO resistance;microarray
Date:	2015-06-20
Issue Date:	2020-08-19 14:12:04 (UTC+8)
Abstract:	臺灣的慢性腎臟疾病和末期腎臟疾病發生率及盛行率在世界各國中始終名列前茅，同時也是台灣人口前十大死因之一。雖然慢性腎臟疾病在台灣的治療已十分完善，在臨床上仍然觀察到一些慢性腎臟病患者病情迅速惡化與腎性貧血患者出現紅血球生成素阻抗性，其原因到目前為止尚未十分清楚。先前的研究指出鈣離子通道的單一核苷酸基因多型性與慢性腎臟疾病有關，鈣池調控型通道的Orai1參與T細胞以及腎小球細胞等非興奮性細胞之鈣池調控鈣離子流入(Store -Operated Calcium Entry, SOCE)，而TRPC3、TRPC4主要參與經受體調控型通道(Receptor-Operated Ca2+ Channel, ROC)引發之鈣離子流入，TRPV5則是體內腎臟鈣離子吸收和再吸收的運輸通道，除了鈣離子運輸外，這些鈣離子通道在發炎反應中亦扮演重要角色。因此，本研究對ORAI1、TRPC3、TRPC4、TRPV5基因多型性與慢性腎臟疾病發展、紅血球生成素阻抗性之相關性進行探討。結果顯示，TRPC3 (rs 10518289)及TRPC3 (rs 906493)皆在基因型分型、顯性遺傳以及對數加成模式與罹患慢性腎臟疾病病人的腎絲球過濾率快速下降有統計上的顯著相關性，這兩個位點分別帶C等位基因(Allele)時GFR可能會下降得較快；另外TRPC3 rs11732666則與紅血球生成素阻抗性有相關性，當病人的rs11732666帶C等位基因(Allele)時會有較高風險產生紅血球生成素阻抗性，故需使用較高劑量之紅血球生成素才能達到療效，本研究顯示TRPC3的基因型變異可能會影響慢性腎臟病的惡化和紅血球生成素阻抗性的產生。 In Taiwan, chronic kidney disease (CKD) and end-stage renal diseases (ESRD) have relatively high incidence and prevalence worldwide. These diseases are also the tenth leading cause of death in Taiwan. The decreasing of glomerular filtration rate (GFR) and increasing of albuminuria are associated with risk of cardiovascular events and all-cause mortality. Although the treatment of CKD in Taiwan has been comprehensively established, some CKD patients with anemia were observed with resistance to high dosage of recombinant human erythropoietin (EPO). Besides, some of them get worse rapidly with unclear reason. Previous studies have indicated that Ca2+ channel transporter genes such as Orai1 and TRPCs are associated with kidney disease and erythropoietin. Orai1 is one of Store-Operated Ca2+ Channel (SOCs) which takes part in store-operated Ca2+ entry (SOCE) on non- excitable cells. TRPC3 and TRPC4 are members of transient receptor potential cation channel super family, and play the role of receptor-operated Ca2+ entry. Furthermore, TRPV5 modulates the absorption and reabsorption of Ca2+ in kidney. These four calcium channel transporters above not only modulate the calcium influx but also involve in inflammation and immune system. Therefore, we conduct a study to figure out the association between polymorphism of calcium channel transporter genes and disease progression as well as EPO resistance among patients with CKD. The results show that two single nucleotide polymorphisms (SNPs) of TRPC3, rs10518289 and rs906493 are significantly associated with the decline of GFR. In addition, our results indicate rs11732666 of TRPC3 is significantly associated with EPO resistance. These findings suggest that the progression of CKD and EPO resistance could be predicted by screening polymorphism of TRPC3.
Description:	碩士指導教授:張偉嶠委員:黃尚志委員:沈麗娟委員:簡淑真
Data Type:	thesis
Appears in Collections:	[Master Program for Clinical Pharmacogenomics and Pharmacoproteomics] Dissertations/Theses

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