Patatin-like phospholipase domain containing 3基因多型性與第二型糖尿病的巨量白蛋白尿之關聯性

The association of Patatin-like phospholipase domain containing 3 gene polymorphism with macroalbuminuria in type 2 diabetes

張維君(Wei-Chun Chang)

指導教授 ： 辛錫璋

高雄醫學大學/醫學院/醫學遺傳學研究所/碩士(2009年)

https://doi.org/10.6832/KMU.2009.00099

摘要

研究背景 : Patatin-like phospholipase domain containing 3 ( PNPLA3 )基因可以製造Adiponutrin，而Adiponutrin是一個存在於脂肪組織的穿膜蛋白。近年已有研究指出PNPLA3基因與肥胖及非酒精性脂肪肝疾病有所關聯性，而肥胖及非酒精性脂肪肝疾病都會增加第二型糖尿病及慢性腎臟疾病的風險性。因此，本研究想探討PNPLA3 rs738409基因多型性變異對第二型糖尿病之發生所扮演的角色，以及此基因多型性是否和糖尿病腎臟病變的嚴重程度也有相關性。
研究設計及方法 :本研究共有1184個受試者，其中826位第二型糖尿病病人為糖尿病組，而358個受試者為非糖尿病對照組。利用即時定量聚合酶連鎖反應方法 (real-time PCR) 分析PNPLA3 rs738409基因多型性的基因分型，也藉由放射性免疫檢定法 (radioimmunoassay) 測量糖尿病病人的尿中白蛋白濃度。
結果：分析非糖尿病控制組及糖尿病組的PNPLA3 rs738409基因多型性， GG、GC和CC基因型之頻率 (13.4%、48.6%、38% vs. 14.0%、51.2%、34.7%)，可知PNPLA3 rs738409基因多型性與第二型糖尿病的發生並無關聯性。將其基因型分組分析臨床生化值，結果發現第二型糖尿病患攜帶GG基因型者，其尿液白蛋白/肌酸酐比值 (615.0±1420.9 mg/gm) 顯著地高於GC基因型 (282.8±908.3 mg/gm)和CC基因型 (218.9±599.4 mg/gm) 兩組 ( p=0.001)。進一步分析PNPLA3 rs738409基因多型性與糖尿病病人的白蛋白尿分組 (正常白蛋白尿組、微量白蛋白尿組及巨量白蛋白尿組)，GG、GC和CC基因型之頻率 (13.6%、49.1%、37.2% vs. 9.7%、56.8%、33.5% vs. 23.3%、48.8%、27.9%)，可發現PNPLA3 rs738409基因多型性變異與糖尿病病人的白蛋白尿嚴重度有所相關 ( p=0.004 )。巨量白蛋白尿組之PNPLA3 rs738409基因多型性分別與正常白蛋白尿組及微量白蛋白尿組比較，在對數回歸分析中證實PNPLA3 rs738409基因多型性對於糖尿病白蛋白尿的嚴重程度是一個獨立的危險因子 (p =0.004, p =0.002)。
結論：本研究結果顯示PNPLA3 rs738409基因多型性與糖尿病白蛋白尿的嚴重程度有關，而且對於巨量白蛋白尿的影響最為顯著，所以此基因多型性在未來或許可作為一個預測腎臟病變的危險因子。

關鍵字

第二型糖尿病 ； 白蛋白尿 ； 白蛋白比肌酸酐的比值 ； PNPLA3 ； 基因多型性

並列摘要

Background : Patatin-like phospholipase domain containing 3 (PNPLA3) encodes the adiponutrin which is a transmembrane protein expressed in adipose tissue. PNPLA3 has previously reported associated with obesity and nonalcoholic fatty liver disease (NAFLD). However, NAFLD and obesity were both associated with increased risks of type 2 diabetes and chronic kidney disease. We explored the role of the PNPLA3 rs738409 single nucleotide polymorphism (SNP) in genetic susceptibility on the development of type 2 diabetes, and whether this SNP is associated with the severity of diabetic albuminuria or not.
Research design and methods : 1184 individuals were evaluated in a case-control association study, which included 826 patients with type 2 diabetes and 358 normoglycemic control subjects . The rs738409 polymorphism of PNPLA3 was genotyped by real-time PCR, and urine albumin concentration was measured by radioimmunoassay.
Results: The PNPLA3 rs738409 SNP was not associated with the development of type 2 diabetes. The mean urine albumin-to-creatinine ratio ( ACR) in the GG group was significantly higher than in the GC and CC groups (615.0±1420.9 vs. 282.8±908.3 and 218.9±599.4 mg/gm, p=0.001). The PNPLA3 rs738409 SNP was associated with diabetic albuminuric status (p =0.004). Multivariate logistic regression analysis showed the PNPLA3 rs738409 SNP to be independently associated with the albuminuric stages of diabetes (macroalbuminuria vs. normoalbuminuria and microalbuminuria, p =0.004 and p = 0.001 ).
Conclusions : This study indicates that the PNPLA3 rs738409 SNP is associated with severity of diabetic nephropathy, especially with macroalbuminuria.

並列關鍵字

type 2 diabetes ； albuminuria ； ACR, albumin-to-creatinine ratio ； Patatin-like phospholipase domain containing 3 ； PNPLA3 ； ploymorphism ； SNP

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