骨保护素基因多态性与重度子痫前期发病的关系

Association between osteoprotegerin gene polymorphisms and severe pre-eclampsia in Chinese women

目的探讨骨保护素基因启动子区163A／G和950T／C位点的多态性与重度子痫前期发病的关系。方法选择2007年7月—2009年3月在四川大学华西第二医院就诊的成都市汉族孕妇共166例。其中重度子痫前期孕妇85例（重度子痫前期组），健康足月孕妇81例（对照组）。应用PCR限制性片段长度多态性（RFLP）技术测定两组孕妇骨保护素基因启动子区163A／G和950T／C位点的基因型及等位基因频率，对两组中不同等位基因孕妇的血压、血肌酐、24h尿蛋白定量、新生儿出生体质量等临床指标进行比较。结果（1）骨保护素基因启动子区163A／G、950T／C位点的基因型及等位基因频率在两组孕妇中的分布均符合Hardy—Weinberg遗传平衡定律。163A／G位点的基因型为AA、AG、GG，等位基因为A、G；950T／C位点的基因型为rrr、TC、CC，等位基因为T、C。（2）重度子痫前期组孕妇163A／G、950T／C位点的基因型、等位基因频率与对照组比较，差异均无统计学意义（P〉0．05）。（3）重度子痫前期组中163A／G位点AG＋GG基因型孕妇血肌酐水平[（76±24）txmol／L]明显高于AA基因型孕妇[（56±18）g^mol／L]，而新生儿出生体质量[（2040±721）g]显著低于AA基因型孕妇[（2520±810）g]，两者比较，差异均有统计学意义（P〈0．05）。对照组中163A／G位点的AG＋GG基因型孕妇血尿素、血肌酐、新生儿出生体质量、新生儿身长等临床指标与AA基因型孕妇比较，差异均无统计学意义（P〉0．05）。（4）重度子痫前期组中950T／C位点的TT基因型孕妇收缩压[（153±16）mmHg（1mmHg=0．133kPa）]、24h尿蛋白定量[（4．0±2．5）g]均显著高于Tc＋CC基因型孕妇[分别为（1454-17）mmHg及（2．9±1．8）g]，两者比较，差异均有统计学意义（P〈0．05）；而对照组中950T／C位点的不同基因型孕妇各临床指标之间比较，差异均无统计学意义（P〉0．05）。结论携带163A／G位点的G等位基因孕妇比携带A等位基因者更具有重度子痫前期遗传易感性；携带950T／C位点的T等位基因孕妇比携带C等位基因者也更具有重度子痫前期遗传易感性。提示骨保护素基因多态性可能与重度子痫前期的发病有关。

Objective To investigate the potential association between 163A/G and 950T/C polymorphisms of osteoprotegerin （OPG） gene and severe pre-eclampsia. Methods Eighty-five severe pre- eclamptic patients and 81 normal term pregnant women （as control group） were recruited from the Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University during the period from July 2007 to March 2009, and they were all Hart population living in Chengdu, China. Genotype and allele frequencies of 163A/G and 950T/C were determined by the PCR-restriction fragment length polymorphism （RFLP） assay. Clinical and biochemical parameters for different alleles between the patients and controls were compared for statistical significance respectively, such as blood pressure, serum creatinine and 24-hour urine protein. Results The observed and expected genotype counts were consistent with Hardy-Weinberg equilibrium. No significant differences were found in the genotype and allele frequencies of 163A/G and 950T/C polymorphisms between the two groups （P 〉 0. 05 ）. However, in the preeclamptic group, serum creatinine was significantly higher in women with the AG ＋ GG genotypes [ （76 ±24） μmol/L] compared with AA genotype [ （56± 18） μmol/L]. Reversely, birth weight was lower in the AG ＋ GG genotypes [ （2040 ± 721） g] than those in the AA genotype [ （2520 ± 810） g], and the P 〈0. 05, respectively. In the severe pre-eclampsia, 950T/C TT genotype carriers exhibited significantly higher systolic blood pressure [（ 153 ＋ 16） mm Hg（ 1 mm Hg = 0. 133 kPa） ] and 24-hour urine protein [ （4.0 ±2. 5） g] compared with TT ＋ TC carriers [ （ 145±17） mm Hg, （2.9 ± 1.8） g], respectively, furthermore the P 〈 0. 05. Conclusions In severe pre-eclampsia, carriers with G allele at position 163A/G has more genetic predisposition than A allele carriers, as well as 950T/C T allele carriers compared with C carriers. Taken together, this study suggested that OPG gene polymorphisms might be associated with some clinical parameters of severe pre-eclampsia.