MIF基因rs1007888位点单核苷酸多态性与妊娠期糖尿病发病的相关性

Association between single nucleotide polymorphism of macrophage migration inhibitory factor-rs1007888 and the pathogenesis of gestational diabetes mellitus

目的探讨巨噬细胞移动抑制因子（MIF）基因rsl007888位点单核苷酸基因多态性（SNP）与妊娠期糖尿病（GDM）发病的相关性。方法选择2011年6月至2012年7月在青岛大学医学院附属医院门诊和住院的120例GDM孕妇为GDM组，同期健康孕妇165例为健康对照组。采用DNA直接测序技术检测两组孕妇的MIF—rs1007888位点基因型，测定两组孕妇空腹血糖（FBG）、空腹胰岛素（FIN）水平、稳态模型胰岛素抵抗指数（HOMA—IR）和稳态模型胰岛B细胞功能指数（HOMA—p），比较两组不同基因型孕妇FBG、FIN、HOMA—IR和HOMA—p的差异。结果（1）GDM组孕妇FBG、FIN水平分别为（5．4±1．2）、（20．5±4．8）mmol／L，较健康对照组[分别为（4．6±0．5）、（13．7±2．9）mmol／L]明显升高，差异均有统计学意义（P均〈0．05）；GDM组HOMA—IR（4．9．4-1．1）高于健康对照组（2．6±0．6），差异有统计学意义（P〈0．05）；GDM组HOMA—B（194±78）低于健康对照组（239±83），差异也有统计学意义（P〈0．05）。（2）两组孕妇MIF—rsl007888位点基因共有3种类型，即GG、GA、AA基因型。GDM组MIF—rsl007888位点GG、GA、AA基因型频率分别为37．5％（45／120）、45．8％（55／120）和16．7％（20／120），G、A等位基因频率分别为60．4％（145／240）、39．6％（95／240）；健康对照组GG、GA、AA基因型频率分别为26．1％（43／165）、54．5％（90／165）和19．4％（32／165），G、A等位基因频率分别为53．3％（176／330）、46．7％（154／330）；GDM组与健康对照组MIF—rs1007888位点各基因型频率比较，差异均有统计学意义（P〈0．05）。GDM组与健康对照组MIF—rs1007888位点各等位基因频率比较，差异均无统计学意义（P〉0．05）。（3）两组共285例孕妇中，GG基因型孕妇（88例）与GA＋AA基因型孕妇（197例）的FBG、FIN、HOMA—IR及HOMA—β分别比较，差异均有统计学意义（P〈0．05）。结论MIF—rs1007888位点SNP与孕妇胰岛素抵抗和胰岛β细胞功能明显相关，而MIF—rsl007888位点GG基因型可能是GDM发病的遗传易感因素。

Objective To investigate the association between single nucleotide polymorphism （SNP） of macrophage migration inhibitory factor （MIF） gene-rs1007888 and the pathogenesis of gestational diabetes mellitus （GDM）. Methods A total of 120 GDM pregnant women （GDM group） and 165 healthy pregnant women （control group ） from Affiliated Hospital of Medical College, Qingdao University were recruited from June 2011 to July 2012. Their age, gestational week, height and weight were recorded. The levels of fasting blood glucose （FBG） and fasting insulin （FIN） were determined. Body mass index （BMI） , the hemeostasis model assessment-insulin resistance （HOMA-IR） and hemeostasis model assessment-β cell function （HOMA-β） were calculated. DNA was extracted from fasting blood samples. SNP of MIF- rs1007888G/A was determined by DNA sequencing. The FBG, FIN, HOMA-IR and HOMA-β were compared between GDM group and tile control group. They were also compared among pregnancies with different genotypes. Results （1） GDM group had higher FBG, FIN and HOMA-IR levels, but lower HOMA-15 than the control group （all P 〈 0. 05）. （2） MIF-rs1007888 SNP genotype frequencies of GG, GA and AA were 37.5% , 45.8% and 16. 7% , and the allelic frequencies of G and A were 60. 4% , 39. 6% in GDM group; However, in the control group, the frequencies of GG, GA and AA were 26. 1% , 54.5% and 19.4%, and the allelic frequencies of G and A were 53.3% , 46. 7% , respectively. The distributions of MIF genotypes in GDM patients were significantly different from the healthy subjects （ P 〈 0. 05 ）. No significant difference of MIF-rs1007888 allele distributions was observed between GDM group and the control group （P 〉0. 05）. （3） The FBG, FIN and HOMA-IR in pregnant women with GG genotype were statistically higher than those with GA or AA genotypes, while HOMA-β was lower in women with GG genotype （ all P 〈 0. 05）. Conclusions The SNP of MIF rs-1007888 was related to the insulin resistance and pancreatic 13 cell function of pregnant women. GG genotype of MIF-rs1007888 might he a genetic susceptible factor in the pathogenesis of GDM.