叶酸MTHFR C677T基因多态性与妊娠早期亚临床甲状腺功能减退的相关性研究
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摘要
目的探讨叶酸MTHFR C677T基因多态性与妊娠早期亚临床甲状腺功能减退的相关性研究。方法回顾性分析2016年12月-2017年12月在本院进行建卡的孕12周内孕妇1 958例的临床资料,其中亚临床甲状腺功能减退215例,单纯性低甲状腺素血症106例,排除其他类型甲状腺疾病后,选取甲状腺功能正常孕早期妇女1 437例作为对照组,筛查叶酸MTHFR C677T基因型及甲状腺激素水平,采用PCR-芯片杂交技术检测MTHFR C677T多态位点基因型,进一步探讨各组间基因型频率及等位基因频率,并分析游离甲状腺素(FT4)、促甲状腺素(TSH)、空腹血糖(GLU)与不同基因型的相关性。结果 3组间,C、T等位基因频率间,无明显差异,而TT型基因明显高于CC型(36. 8%对11. 7%,40. 0%对18. 7%,52. 2%对9. 2%,P <0. 05);且游离甲状腺素(FT4)(13. 01±1. 30) pmol/L在TT型基因型中明显低于CC型(13. 68±3. 68) pmol/L、CT型(13. 27±1. 87) pmol/L及CC+CT组合(13. 39±2. 49) pmol/L(P <0. 05)。结论低FT4与突变型TT型基因相关,可以做为叶酸MTHFR C677T基因多态性与妊娠早期亚临床甲状腺功能减退的相关性研究的有力依据。
Objective To study the correlation of MTHFR C677 T gene polymorphism in folic acid with subclinical hypothyroidism in early pregnancy. Methods To retrospectively analyze 1 958 pregnant women at 12 weeks of pregnancy from December2016-December 2017,including 215 cases of subclinical hypothyroidism,106 cases of simple hypothyroxinemia. After excluding other types of thyroid disease,1 437 pregnant women with normal thyroid function were selected as the control group.The folic acid MTHFR C677 T genotype and thyroid hormone levels were detected,and the MTHFR C677 T polymorphic locus genotype was detected by PCR-chip hybridization. The genotype frequency and allele frequency were further studied between groups,and the correlation of free thyroxine( FT4),thyrotropin( TSH),fasting blood glucose( GLU) with different genotypes was analyzed. Results There was no significant difference between C and T allele frequencies among the three groups. TT type gene was significantly higher than CC type gene( 36. 8% vs 11. 7%,40. 0% vs 18. 7%,52. 2% vs 9. 2%,P < 0. 05); free thyroxine( FT4)( 13. 01 ± 1. 30) pmol/L in TT genotype was significantly lower than CC type( 13. 68 ± 3. 68) pmol/L,CT type( 13. 27 ± 1. 87) pmol/L and CC + CT combination( 13. 39 ± 2. 49) pmol/L( P < 0. 05). Conclusion Low FT4 is associated with mutant TT-type genes and can be used as a strong basis for the study of the relationship between folate MTHFR C677 T gene polymorphism and subclinical hypothyroidism in early pregnancy.
Objective To study the correlation of MTHFR C677 T gene polymorphism in folic acid with subclinical hypothyroidism in early pregnancy. Methods To retrospectively analyze 1 958 pregnant women at 12 weeks of pregnancy from December2016-December 2017,including 215 cases of subclinical hypothyroidism,106 cases of simple hypothyroxinemia. After excluding other types of thyroid disease,1 437 pregnant women with normal thyroid function were selected as the control group.The folic acid MTHFR C677 T genotype and thyroid hormone levels were detected,and the MTHFR C677 T polymorphic locus genotype was detected by PCR-chip hybridization. The genotype frequency and allele frequency were further studied between groups,and the correlation of free thyroxine( FT4),thyrotropin( TSH),fasting blood glucose( GLU) with different genotypes was analyzed. Results There was no significant difference between C and T allele frequencies among the three groups. TT type gene was significantly higher than CC type gene( 36. 8% vs 11. 7%,40. 0% vs 18. 7%,52. 2% vs 9. 2%,P < 0. 05); free thyroxine( FT4)( 13. 01 ± 1. 30) pmol/L in TT genotype was significantly lower than CC type( 13. 68 ± 3. 68) pmol/L,CT type( 13. 27 ± 1. 87) pmol/L and CC + CT combination( 13. 39 ± 2. 49) pmol/L( P < 0. 05). Conclusion Low FT4 is associated with mutant TT-type genes and can be used as a strong basis for the study of the relationship between folate MTHFR C677 T gene polymorphism and subclinical hypothyroidism in early pregnancy.
引文
[1]吴美琴,王伟业,颜崇淮.妊娠期亚临床甲状腺功能减退的相关指南对比分析[J].现代妇产科进展,2017,2(18):145-148.
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[9] Blatt AJ,Nakamoto JM,Kaufman HW. National status of testing for hypothyroidism during pregnancy and postpartum[J]. J Clin Endocrinol Metab,2012,97(3):777-784.
[10]李春莉,黄卉,李秋红.妊娠早期亚临床甲状腺功能减退与妊娠糖尿病的相关性研究[J].中华内分泌代谢杂志,2014,30(9):747-748. DOI:10. 3760/cma. j. issn. 1000-6999. 2014. 09. 006.
[11] Mehran L,Amouzegar A,Tohidi M,et al. Serum free thyoxine concentration is Associated with metabolic syndrome in euthyroid subjects[J]. Thyroid,2017,27(7):886-893.
[12]李华,黄娟娟.亚甲基四氢叶酸还原酶基因677多态性与复发性流产相关性分析[J].陕西医学杂志,2017,46(7):855-857.
[13]潘伟,冯晓萍,俞磊.叶酸代谢相关酶系基因多态性与不良孕史的相关性研究[J].中国妇产科临床杂志. 2017,18(4):332-335.
[14]崔会玲,鲁衍强,马少杰,等.郑州市汉族女性MTHFR和MTRR基因多态性分布[J].中南大学学报:医学版,2015,58(7):710-714.
[15]李春莉,余浪,李秋红.妊娠早期单纯低甲状腺血症与妊娠期糖尿病相关性分析[J].中华内分泌代谢杂志,2017,33(3):194-197.
[2]庄寒秋,蒋艳敏,许岚,等.孕妇妊娠期甲状腺功能减退对妊娠结局及胎儿的影响[J].中国妇幼保健,2017,12(24):6104-6106.
[3]朱晓琴,鲁衍强,王慧,等.淮安市汉族女性MTHFR和MTRR基因多态性研究[J].中国妇幼保健,2017,12(24):6222-6226.
[4]曹建军,方锴,杨焕明.生殖遗传新技术与生殖安全重点专题—基因组学在预防出生缺陷中的应用[J].计划生育学杂志,2013,6(32):415-418.
[5]中华医学会内分泌学分会,中华医学会围产医学分会.妊娠和产后甲状腺疾病诊治指南[J].中华内分泌代谢杂志,2012,28(2):354-371.
[6]商广芸,王宏宇,刘金波,等.亚甲基四氢叶酸还原酶C677T基因多态性与2型糖尿病关系的病例对照研究[J].医学研究杂志,2017,46(9):72-76.
[7]尚丽新,关怀.妊娠合并内分泌疾病发病情况及对母儿的危害[J].人民军医,2014,57(7):805-807
[8]单忠艳.《中国甲状腺疾病诊治指南》导读[J].中国实用内科杂志,2008,28(4):260-261.
[9] Blatt AJ,Nakamoto JM,Kaufman HW. National status of testing for hypothyroidism during pregnancy and postpartum[J]. J Clin Endocrinol Metab,2012,97(3):777-784.
[10]李春莉,黄卉,李秋红.妊娠早期亚临床甲状腺功能减退与妊娠糖尿病的相关性研究[J].中华内分泌代谢杂志,2014,30(9):747-748. DOI:10. 3760/cma. j. issn. 1000-6999. 2014. 09. 006.
[11] Mehran L,Amouzegar A,Tohidi M,et al. Serum free thyoxine concentration is Associated with metabolic syndrome in euthyroid subjects[J]. Thyroid,2017,27(7):886-893.
[12]李华,黄娟娟.亚甲基四氢叶酸还原酶基因677多态性与复发性流产相关性分析[J].陕西医学杂志,2017,46(7):855-857.
[13]潘伟,冯晓萍,俞磊.叶酸代谢相关酶系基因多态性与不良孕史的相关性研究[J].中国妇产科临床杂志. 2017,18(4):332-335.
[14]崔会玲,鲁衍强,马少杰,等.郑州市汉族女性MTHFR和MTRR基因多态性分布[J].中南大学学报:医学版,2015,58(7):710-714.
[15]李春莉,余浪,李秋红.妊娠早期单纯低甲状腺血症与妊娠期糖尿病相关性分析[J].中华内分泌代谢杂志,2017,33(3):194-197.