妊娠期糖尿病患者肿瘤坏死因子-α基因多态性的实验性研究

Study on relationship between level of tumor necrosis factor alpha and gene polymorphism in patients with gestational diabetes mellitus

目的研究东北汉族妊娠期糖尿病(GDM)孕妇肿瘤坏死因子-α(TNF-α)基因多态性的分布频率及在GDM发病中的作用。方法选取120例GDM作为病例组,120例糖耐量正常的孕妇作为对照组,采用双抗体夹心酶联免疫吸附试验(ELISA)检测血清TNF-α水平,以稳态模型Homa model公式评估胰岛素抵抗(IR),同时应用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)技术,检测TNF-α基因-308和-238位点等位基因和基因型的分布频率。结果⑴GDM组及对照组的血清TNF-α水平分别为(10.29±2.44)μg/L和(5.21±1.01)μg/L(P<0.05);FINS分别为(24.34±12.84)mIU/L和(17.88±7.31)mIU/L(P<0.01);HOMA-IR分别为(2.74±1.06)和(1.35±0.69)(P<0.01)。⑵GDM组-238多态性位点A等位基因频率(0.0583和0.0417)及GA+AA基因型频率(0.1083和0.0917)均高于正常妊娠对照组,但差异无统计学意义(P>0.05)。GDM组-308多态性位点A等位基因频率(0.1375和0.0583)及GA+AA基因型频率(0.2417和0.1167)显著高于正常妊娠对照组,差异有统计学意义(P<0.05)。⑶GDM组GA+AA基因组及GG基因型组TNF-α分别为[(6.35±1.43)μg/L]和[(5.68±0.45)μg/L](P<0.05);FINS分别为(13.42±4.73)mIU/L和(10.40±3.63)mIU/L(P<0.01);HOMA-IR分别为(7.42±1.93)和(4.11±1.31)(P<0.01)。结论我国东北汉族孕妇人群中,TNF-α基因308G→A变异可增加孕妇患妊娠期糖尿病的危险性。A等位基因可能通过增加TNF-α的释放参与胰岛素抵抗,导致GDM的发病。

Objectlve：To investigate tumor necrosis factor alpha gene polymorphism in patients with gestational diabetes mellitas in Hans of Northeast Chinese population.Methods： 120 women with GDM, 120 health pregnancy women were studied. Serum TNF- α was measured by ELISA.IR was assessed by Homo model,C, enotype of TNF- α was determined by PCB- RFLP.Besuhs：（l）In CDM and NCT Serum TNF- α level were （10.29 ± 2.44） μg/L and （5.21 ± 1.01 ） μg/L （ P 〈 0.05） respectively;Serum FINS level were（24.34 ± 12.84 ） mIU/L and（ 17. 88 ± 7.31 ） mIU/L （ P 〈 0.01 ） respectively ; HOMA - Ilt （2.74 ± 1.06） 和 （ 1.35 ± 0.69） （ P 〈 0.01 ） respectively. （2）TNF - α gene G238A allele in CDM and control groups were （0.0583 和 0.0417）, and frequencies of CA ＋ AA genotype were （0.1083 和 0.0917） （ P 〉 0. 05）, respectively. TNF- α gene G308A allele in CDM and control groups were 0. 1375 和 0.0583） ,and frequencies of CA ＋ AA genotype were （0.2417 和 0.1167）（ P 〈 0.05）, respectively. （3）In CA ＋ AA genotype group and GG genotype group of CDM, serum TNF- α level were [（6.35± 1.43） μg/L]and[（5.68 ±0.45） μg/L] （P 〈 0.05） ;FINS（13.42 ± 4.73） mIU/L and （10.40±3.63） mIU/L（P 〈0.01） respectively; HOMA - IB（7.42 ± 1.93 ） and （4.11 ± 1.31 ） （ P 〈 0.01 ） respectively. Conclusion： In Hans of Northeast Chinese population, TNF - α gene G308A mutation increases the risk of CDM. A allele may be involved in IR and pathogenesis of CDM by increasing the release of TNF- α.