巨噬细胞移动抑制因子-173G／C位点多态性与重度子痫前期发病及胰岛素抵抗的关系

Association between severe preeclampsia and single nucleotide polymorphism of macrophage migration inhibitory factors - 173G/C

目的探讨巨噬细胞移动抑制因子（MIF）-173G／C位点单核苷酸多态性（SNP）与重度子痫前期发病及胰岛素抵抗的关系。方法选择2010年3月至2011年3月在青岛大学医学院附属医院住院的重度子痫前期孕妇124例（子痫前期组），选取同期健康晚期妊娠孕妇160例为对照组。采用荧光染料PCR技术检测两组孕妇MIF-173G／C位点的SNP，比较两组孕妇基因型频率、等位基因频率的差异。测定两组孕妇的空腹血糖（FBG）、空腹胰岛素（FIN）和总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）水平，采用稳态模型评估法计算的胰岛素抵抗指数（HOMA—IR）评估胰岛素抵抗程度，记录孕前体质指数（BMI），比较不同基因型子痫前期组及对照组孕妇FBG、FIN、TC、TG、HDL、LDL、BMI及HOMA—IR的差异。结果（1）MIF-173G／C位点多态性：共检出3种基因型；子痫前期组GG、CG和CC基因型频率分别为62．1％（77／124）、30．6％（38／124）和7．3％（9／124），G、C等位基因频率分别为77．4％（192／248）、22．6％（56／248）；对照组GG、CG和CC基因型频率分别为64．4％（103／160）、30．6％（49／160）和5．0％（8／160），G、C等位基因频率分别为79．7％（255／320）、20．3％（65／320）。两组间各基因型频率及等位基因频率分别比较，差异均无统计学意义（P〉0．05）。（2）子痫前期组内CG、CC基因型孕妇BMI[（25±4）kg／m^2]高于GG基因型孕妇[（22±4）kg／m^2]，差异有统计学意义（t=3．96，P〈0．05）。（3）子痫前期组内CG、CC基因型孕妇FIN及HOMA—IR[分别为（15．7±2．9）mmol／L、3．3±0．5]均高于GG基因型患者[分别为（13．6±4．0）mmol／L、2．7±0．6]，分别比较，差异均有统计学意义（t值分别为3．17、5．58，P〈0．05）。（4）子痫前期组内不同基因型孕妇FBG、TC、TG、HDL、LDL水平比较，差异均无统计学意义（P〉0．05）。结论MIF-173G／C位点SNP与重度子痫前期胰岛素抵抗密切相关，但该位点可能不是子痫前期孕妇发病的易感基因位点；CG和CC基因型加重了重度子痫前期胰岛素抵抗的程度。

Objective To investigate whether single nucleotide polymorphism （SNP） of macrophage migration inhibitory factor （MIF） gene -173G/C is associated with severe preeclampsia. Methods Totally 124 severe preeclampsia patients and 160 healthy pregnant women （control group） were included in our study who were recruited consecutively from Affiliated Hospital of Qingdao University Medical College between March 2010 and March 2011. The SNP was detected through SYBR Green PCR. The levels of fasting blood glucose （FBG） , fasting insulin （FIN） , and serum total cholesterol （ TC）, triglyceride （TG） , high density lipoprotein （HDL） and light density lipoprotein （LDL） were determined in every participants. The homeostasis model assessment-insulin resistance （HOMA-IR） was calculated. The allele and genotype frequencies between severe preeclampsia patients and control group were compared. The FBG, FIN, body mass index （BMI）, HOMA-IR, TC, TG, HDL and LDL in different genotype were compared. Results （ 1 ）The MIF - 173G/C SNP genotype frequencies of GG, CG, and CC were 62. 1% （77/124）, 30.6% （38/124）, 7.3% （9/124）, the allelie frequencies of G and C were 77.4% （192/248） and 22.6% （56/248）, respectively, in severe preeclampsia patients; the MIF - 173G/C SNP genotype frequencies of GG, CG, and CC were 64. 4% （103/160） , 30. 6% （49/160） , 5.0% （8/160） , the allelie frequencies of G and C were 79. 7% （255/320） and 20. 3% （65/320）, respectively, in the control group. No significant differences were observed in the genotypes and allele distributions of MIF - 173G/C SNP between the severe preeclampsia patients and control group （all P 〉 0. 05 ）. （2） The severe preeclampsia patients with CG and CC genotypes had higher BMI compared with the GG genotype [ （25 ± 4） versus （22 ± 4） kg/m^2 ; t = 3.96, P 〈 0. 05 ]. （ 3 ） The severe preeclampsia patients with CG and CC genotypes had higher FIN level and higher HOMA-IR compared with the GG genotype [ （ 15.7 ±2.9） versus （ 13.6±4. 0） mmoL/L, 3.3 ±0. 5 versus 2.7 ± 0.6 ; t = 3.17, t = 5.58, all P 〈 0.05] （4） There was no significant difference in FBG, TC, TG, HDL and LDL levels in severe preeclampsia patients with different genotypes （ all P 〉 0. 05 ）. Conclusions The present study suggests that the MIF - 173G/C SNP is associated with insulin resistance in severe preeclampsia patients. The CG and CC genotypes increase the degree of insulin resistance, but it is may not associate with susceptibility among severe preeclampsia patients of Hart Chinese women.