高脂血症性急性胰腺炎脂蛋白脂酶基因多态性研究

目的 探讨三酰甘油分解代谢酶脂蛋白脂酶(LPL)的表达和基因多态性与高脂血症性急性胰腺炎(HLP)的相关性.方法 2005年5月至2006年12月HLP住院患者20例,急性胰腺炎患者50例,另选取血脂正常患其他疾病者50例为对照.测定血清三酰甘油(TG)、胆固醇(Ch)、游离脂肪酸(FFA)、脂蛋白数值、血清LPL/肝脂酶(HL)活性;RT-PCR检测LPL mRNA表达;聚合酶链-限制性酶切片段多态性分析(PCR-RFLP)法分析LPL基因内含子8 Hind Ⅲ基因多态性变化.结果 HLP组血清TG、胆固醇(Ch)和FFA测定值均显著高于AP组和对照组,差异均有统计学意义(P值均<0.05);HLP组ApoE值显著高于AP组和对照组(P<0.05);HLP组高密度脂蛋白(HDL)显著低于对照组(P<0.05).HLP组LPL值为(5.98±2.28)U/L,均显著高于AP组和对照组(1.97±0.76)U/L和(1.04±0.53)U/L,P值分别=0.046和0.031];HLP组HL值为(8.15±2.86)U/L,均显著高于AP组和对照组(1.64±0.59)U/L和(0.86±0.39)U/L,P值分别=0.002和0.001].HLP组LPL mRNA表达高于AP组,差异有统计学意义(P=0.0325).LPL基因内含子8 Hind Ⅲ分析,H2等位基因频率HLP组显著高于对照组(0.90比0.72,P<0.05);H1等位基因频率在HLP和AP组均显著低于对照组(0.10比0.28和0.14比0.28,P<0.05).HLP组H2H2基因型患者TG和Apo E值均显著高于H2H1/H1H1基因型(P值分别=0.043和0.046);AP组H2H2基因型患者TG值显著高于H2H1/H1H1基因型(P=0.032).结论 HLP患者LPL Hind Ⅲ H2等位基因频率显著高于正常人群,主要与高三酰甘油血症(HTG)相关,而与胰腺炎无关;且H2H2基因型的HLP患者血清TG、ApoE值高于其他基因型者.HTG可引起LPL基因和蛋白表达活性增高,加速TG大量分解代谢和FFA等分解产物蓄积,是诱发和加重HLP的中心环节和重要病理生理机制.

Gene polymorphism of lipoprotein lipase in patients with acute hypedipidemic pancreatitis

Objective To investigate the expression and polymorphism of lipoprotein lipase (LPL) gene and their association with acute hyperlipidemic pancreatitis(HLP). Methods A total of 120 patients Were assigned to HLP group (n=20), acute pancreatitis (AP) group (n=50) and control group (n= 50). Serum levels of triglyceride (TG), cholesterol (Ch), free fatty acid (FFA), lipoprotein and apolipoprotein and serum LPL/HL activities were determined. The mRNA expressions of LPL/HL and LPL gene intron 8 polymorphisms were detected by RT-PCR and PCR-RFLP, respectively. Results The serum levels of TG, Ch, FFA and ApoE were significantly higher in HLP group than those in AP group and control group (P<0.05). The serum level of HDL was lower in HLP group than that in AP group and control group(P<0.05). The serum LPL/HL activities were significantly higher in HLP group than that in AP and control groups. The expression of LPL mRNA was up-regulated and intron 8 Hind Ⅲ H2 allele frequency was significantly inereased in the HLP group compared to control group(0.90/0.72, P<0.05). H1 allele frequency was significantly decreased in the HLP and AP groups compared to control group(0.10/0.28 and 0.14/0.28, respectively). Conclusions The high allele frequency of LPL gene intron 8 Hind H2 result in the increase of activities and expression of LPL mRNA, which exacerbate the development of HLP through changing TG metabolism such as FFA accumulation.