目的:探究子痫前期(PE)患者血脂、脂蛋白、载脂蛋白水平的变化,并用聚合酶链式反应及限制性片段长度多态性(PCR-RFLP)方法研究LPL基因HindⅢ和PvuⅡ酶切位点多态性与PE的关系,从遗传学角度探讨其在PE发生中的作用。 方法:按照乐杰主编《妇产科学》第7版标准选取PE患者142例作为实验组,并收集157例同期正常妊娠妇女作为对照组,测定其血脂、脂蛋白、载脂蛋白水平,采用PCR-RFLP方法检测两组LPL基因HindⅢ和PvuⅡ酶切位点的多态性。结果:(1) 实验组甘油三酯(TG)、总胆固醇(TC)及载脂蛋白B(ApoB)均明显高于对照组(P<0.01), 低密度脂蛋白(LDL)亦高于对照组(P<0.05);高密度脂蛋白(HDL)低于对照组(P>0.05),其中的脂质成分LP(a)高于正常组(P>0.05);载脂蛋白A1(ApoA1)低于对照组(P<0.01)。PE组动脉粥样硬化指数-HDL)/HDL,AI]较对照组显著升高(P<0.01)。(2) LPL基因HindⅢ酶切位点H+H+、 H+H-、H-H-基因型,实验组分别为117(82.4%)、19(13.4%)和6(4.2%),对照组分别为108(68.8%)、36(22.9%)和13(8.3%)。实验组等位基因H+ 253(89.1%)、H- 31(10.9%),对照组等位基因 H+ 252(80.3%)、H- 62(19.7%)。基因型及等位基因分布频率组间比较P值均小于0.05(基因型P=0.024,等位基因P=0.003),差异有统计学意义。而LPL基因PvuⅡ酶切位点基因型(P+P+,P+P-,P-P-)及等位基因(P+,P-)分布频率在实验组与对照组之间差异无统计学意义(基因型P=0.86,等位基因P=0.528)。(3) LPL-HindⅢ实验组和对照组各基因型之间血脂水平差异显著,H+H+基因型的TC、TG、LDL、ApoB及(TC-HDL)/HDL明显高于另两种基因型(P<0.01),HDL及ApoA1低于另两种基因型(P<0.01),Lp(a)差异无统计学意义(P>0.05)。实验组和对照组LPL-PvuⅡ各基因型间血脂水平差异均无统计学意义(P>0.05)。结论:(1) PE患者存在明显脂质代谢异常,并具有动脉粥样硬化高风险。(2) LPL基因HindⅢ位点多态性影响个体血脂水平,H+H+基因型携带者存在明显的脂质代谢异常。(3) LPL基因HindⅢ酶切位点多态性与PE的发生存在一定相关性,携带H+等位基因的孕妇可能更易发展成为PE。PvuⅡ酶切位点的基因多态性与血脂水平及PE的发生无明显关联。 |
Objective: To study the level of serum lipid, lipoprotein, apolipoprotein of preeclampsia(PE) patients, using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method to study the relationship between lipoprotein lipase( LPL) gene HindⅢ and PvuⅡ polymorphisms and PE, probing into its role in the onset and development of PE from a heredity angle. Methods: Level of serum lipid,lipoprotein, apolipoprotein and LPL gene HindⅢ and PvuⅡ polymorphisms were studied using automatic biochemistry analyzer and PCR-RFLP separately in 142 PE pregnant women as PE group and 157 healthy pregnant women as control group.Results: (1) PE group has higher triglycerides (TG),total cholesterol(TC),apolipoprotein B(ApoB)(P<0.01),so does low-density lipoprotein (LDL)(P<0.05) and lower apolipoprotein A1(ApoA1)(P<0.01) than control group. High-density lipoprotein (HDL) of PE group was lower and of which the lipoprotein (Lp(a)) higher than control group,but both have no statistical differences(P>0.05).PE group had significantly higher atherosclerotic index(AI)(P<0.01) than control group.(2) PE group had 117(82.4%) women with H+H+ genotype, 19(13.4%) women with H+H- and 6(4.2%) women with H-H-. The control group had 108(68.8%) women with H+H+ genotype, 36(22.9%) women with H+H- and 13(8.3%) women with H-H-. The PE group had 266(89.3%) of H+, 32(10.7%) of H-.The control group had 252(80.3%) of H+, 62(19.7%) of H-. There was a statistical significance in the distribution of both genotype and allelic frequency between groups (genotype P=0.024, allele P=0.003). The PvuⅡ polymorphism of LPL gene had no statistical significance both in distribution of genotype and allelic frequency between the PE and control group (genotype P=0.86, allele P=0.528).(3) Pregnant women with LPL gene H+H+ genotype had higher TC,TG,LDL, ApoB and AI(P<0.01) and lower HDL and ApoA1(P<0.05) than whom with H+H- or H-H- genotype in both groups. While there was no difference in serum Lp(a) level(P>0.05).No statistical difference of serum lipid level had been found in each genotype of LPL gene PvuⅡ in both groups. Conclusion: (1) PE patients have obvious dyslipidemia and a high risk of atherosclerosis.(2) LPL gene HindⅢ polymorphism affects serum lipid level in individuals.(3) LPL gene HindⅢ polymorphism has some relationship with the occurance of PE. The H+ carrier may be easier to develop to be PE patient when pregnant. While the PvuⅡ polymorphism and allele P+ have no signifigant relationship with PE. |
[1] 乐杰.妇产科学[M].7版.北京:人民卫生出版社,2008:92.
[2] WANG X L,McCREDIE R M,WILCKEN D E.Common DNA polymorphisms at the lipoprotein lipase gene:association with severity of coronary artery disease and diabetes[J].Circulation,1996,93(7):1339-1345.
[3] MEAD J R,IRVINE S A,RAMJI D P.Lipoprotein lipase:structure,function, regulation,and role in disease[J].J Mol Med,2002,80:753-769.
[4] VILLA P M,LAIVUORI H,KAJANTIE E,et al.Free fatty acid profiles in preeclampsia[J].Prostaqlandins Leukot Essent Fatty Acids,2009,81(1):17-21.
[5] TIAN Y,LONG S Y,XU Y H,et al.Study on ApoE gene polymorphism and subclasses of serum high density lipoprotein in type Ⅳ hyperlipidemia[J].Chinese J Med Genetics,2005,22(1):96-98.
[6] RAY J G,DIAMOND P,SINGH G,et al.Brief overview of maternal Iriglycerides as a risk factor for preeclampsia[J].BJDG,2006,113(4):379-386.
[7] BELO L,CASLAKE M,GAFFNEY D,et al.Changes in LDL size and HDL concentration in normal and pre-eclampsia pregnancies[J].Atherosclerosis,2002,162(2):425-432.
[8] 徐友娣,殷惠蓉.妊娠高血压综合征与脂类、载脂蛋白、血浆蛋白代谢的关系[J].现代医学,2003,31(6):390-391.
[9] BIRKELAND K I,KILHOVD B,THORSBY P,et al.Heterogeneity of non-insulin-dependent diabetes expressed as variability in insulin sensitivity,beta-cell function and cardiovascular risk profile[J].Diabet Med,2003,20(1):37-45.
[10] LONG S Y,TIAN Y,ZHANG R,et al.Relationship between plasma HDL subclasses distribution and lipoprotein lipase gene HindⅢpolymorphism in hyperlipidemia[J].Clin Chim Acta,2006,366(1-2):316-321.
[11] MA Y Q,THOMAS G N,NG M C,et al.The lipoprotein lipase gene HindⅢpolymorphism is associated with lipid levels in early-onset type 2 diabetic patients[J].Metabolism,2003,52(3):338-343
[12] 苏慧,黄晨,孙新,等.LPL基因HindⅢ多态性与高脂血症和冠心病的关系[J].心脏杂志,2005,17(6):599-601.
[13] 孙琳,陈璐璐,耿厚法,等.LPL基因多态性与2型糖尿病合并脑血管病变及血脂的关系[J].山东大学学报:医学版,2009,47(8):5-9.
[14] 杨志明,郭淑霞,张景玉,等.HindⅢ、S447X基因多态性与哈萨克族MS关系[J].中国公共卫生,2010,16(6):705-707.
[15] CHAMBERLAIN J C,THORN J A,OKA K,et al.DNA polymorphisms at lipoprotein lipase gene:Associations in normal and hypertriglyceridaemia subjects[J].Atherosclerosis,1989,79(1):85-91.
[16] COLAGIURI S.Lipoprotein lipase gene may shape diabetic future[J].CA Lancet,1997,350:269-273.
[17] 樊芸,张蓉,刘秉文,等.中国人内源性高甘油三酯血症与脂蛋白脂酶基因PvuⅡ多态性关联的研究[J].中华医学遗传学杂志,2001,18(4):296.
[18] 崔晓栋,姜妙娜,宋林萱.2 型糖尿病及胰岛素抵抗与脂蛋白脂酶基因HindⅢ和PvuⅡ酶切位点多态性相关性的研究[J].中国慢性病预防与控制,2007,15(6):532.
[19] 李建新,李焱,黄越玲,等.妊高征与脂蛋白酯酶基因PvuⅡ多态性与血脂指标关系[J].解剖学研究,2006,28(4):28-283. |
