【摘要】：[目的]對(duì)一個(gè)漢族2型糖尿病家系的臨床特征和遺傳強(qiáng)度進(jìn)行評(píng)價(jià)。并應(yīng)用人類抗體芯片(Antibody Microarray)技術(shù)篩選家系人群的相關(guān)目標(biāo)因子,獲得一種或幾種差異表達(dá)的酪氨酸激酶,探討家族聚集性糖尿病的分子機(jī)制。[方法]對(duì)先證者及家系中糖尿病患者的臨床特征進(jìn)行分析,通過計(jì)算家系先證者同胞中糖尿病患病危險(xiǎn)性(λs值),評(píng)價(jià)該家系的遺傳強(qiáng)度。從15名家系成員中,挑選出3名入選者進(jìn)行磷酸化抗體芯片檢測(cè)。其中,先證者及其子代糖尿病患者作為研究對(duì)象,家系中血糖正常者及同地區(qū)無親緣關(guān)系正常者各1人作為對(duì)照,運(yùn)用標(biāo)記有71種目標(biāo)因子RayBiotech AAH-PRTK-1-4,檢測(cè)家系中2型糖尿病患者血清酪氨酸激酶差異性表達(dá)。[結(jié)果]1.該家系共4代,直系親屬15人,確診糖尿病病例7例,男3例、女4例,其臨床特征表現(xiàn)為：①發(fā)病年齡30-55歲,均無明顯“三多一少”癥狀,無自發(fā)酮癥傾向；②除Ⅱ-1、Ⅲ-1外,另外5名糖尿病患者BMI均24kg/m2；③除Ⅲ-1外,男性患者腰圍均90cm、女性患者腰圍均80cm；男性患者腰臀比均0.9、女性患者腰臀比均0.85；④除新發(fā)現(xiàn)的Ⅱ-6未進(jìn)行糖尿病治療外,Ⅱ-1、Ⅲ-1開始啟用胰島素治療,余4名患者口服降糖藥物治療。2.該家系人群結(jié)構(gòu)較全面,親屬為糖尿病高危人群,遺傳強(qiáng)度λs=8.59,具有很強(qiáng)的家族聚集性,適合作為進(jìn)一步研究遺傳因素的目標(biāo)人群。3.先證者及其子代糖尿病患者(Ⅱ-1、Ⅲ-1)相關(guān)生化指標(biāo)顯示：總膽固醇、低密度脂蛋白、甘油三酯均高于正常,高密度脂蛋白均低于正常,提示存在血脂代謝異常。4.應(yīng)用RayBiotech AAH-PRTK-1-4對(duì)家系中2型糖尿病患者、家系中血糖正常者及同地區(qū)無親緣關(guān)系正常者的血清樣本進(jìn)行檢測(cè),觀察到6個(gè)差異表達(dá)的酪氨酸激酶,包括FGFR2(a isoform)、NGFR、 ROR1、 ROR2、TNK1 和VEGF R2在家系中2型糖尿病患者血清中表達(dá)高于家系中血糖正常者及同地區(qū)無親緣關(guān)系正常者1.5倍以上。[結(jié)論]1.該家系具有明顯家族聚集和遺傳傾向,且家系中糖尿病患者均存在中心性肥胖。2.就該家系中選取的3名研究對(duì)象而言,兩名2型糖尿病患者的體重指數(shù)、腰臀比、甘油三酯、總膽固醇、低密度脂蛋白明顯高于血糖正常者,高密度脂蛋白低于血糖正常者。3.高通量RayBiotech AAH-PRTK-1-4檢測(cè)顯示,家系中2型糖尿病患者、家系中血糖正常者及同地區(qū)無親緣關(guān)系正常者血清存在酪氨酸激酶磷酸化水平差異。其中,表達(dá)明顯高于家系中血糖正常者及同地區(qū)無親緣關(guān)系正常者的有6個(gè)酪氨酸激酶,即FGFR2 (a isoform)、NGFR、ROR1、ROR2、 VEGFR2、TNK1,它們可能參與家族性糖尿病的發(fā)病過程。
[Abstract]:Objective] to evaluate the clinical characteristics and genetic strength of a Han Chinese family with type 2 diabetes mellitus. Human antibody chip (Antibody Microarray) technique was used to screen the relative target factors of family population to obtain one or several differentially expressed tyrosine kinases and to explore the molecular mechanism of familial aggregation diabetes. [methods] the clinical characteristics of the patients with diabetes mellitus in the proband and the families were analyzed, and the genetic strength of the families was evaluated by calculating the risk of diabetes (位 s) among the proband sibling of the families. Three of the 15 family members were selected for phosphorylation antibody chip test. Among them, the patients with diabetes mellitus of proband and their offspring were used as the research objects, and the subjects with normal blood glucose in their families and those with no related relationship in the same region were used as control. RayBiotech AAH-PRTK-1-4 was used to detect the differential expression of serum tyrosine kinase in patients with type 2 diabetes mellitus. [result] 1. There were 15 direct relatives in this family, 7 cases of diabetes mellitus were diagnosed, 3 cases of male and 4 cases of female. The clinical features of this family were 30 to 55 years old, with no obvious symptoms of "three more than one less" and no tendency of spontaneous ketosis. (2) except 鈪，

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