[1]朱 琳,陈跃瑜,林延润,等.PCOS 患者MTHFR C677T 基因多态性与胰岛素峰值后移的相关性研究[J].现代检验医学杂志,2023,38(06):54-58+141.[doi:10.3969/j.issn.1671-7414.2023.06.010]
 ZHU Lin,CHEN Yueyu,LIN Yanrun,et al.Relationship between MTHFR C677T Polymorphism and Insulin Peak Shift in Patients with PCOS[J].Journal of Modern Laboratory Medicine,2023,38(06):54-58+141.[doi:10.3969/j.issn.1671-7414.2023.06.010]
点击复制

PCOS 患者MTHFR C677T 基因多态性与胰岛素峰值后移的相关性研究()
分享到:

《现代检验医学杂志》[ISSN:/CN:]

卷:
第38卷
期数:
2023年06期
页码:
54-58+141
栏目:
论著
出版日期:
2023-11-15

文章信息/Info

Title:
Relationship between MTHFR C677T Polymorphism and Insulin Peak Shift in Patients with PCOS
文章编号:
1671-7414(2023)06-054-06
作者:
朱 琳陈跃瑜林延润杨发达
(佛山市南海区妇幼保健院检验科, 广东佛山 528200)
Author(s):
ZHU LinCHEN YueyuLIN YanrunYANG Fada
(Department of Clinical Laboratory ,Nanhai District Maternal and Child Health Hospital of Foshan City,Guangdong Foshan 528200, China)
关键词:
多囊卵巢综合征亚甲基四氢叶酸还原酶胰岛素释放试验胰岛素峰值后移
分类号:
R711.75;Q786
DOI:
10.3969/j.issn.1671-7414.2023.06.010
文献标志码:
A
摘要:
目的 探讨多囊卵巢综合征(polycystic ovary syndrome,PCOS)患者亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase,MTHFR)C677T 基因多态性与胰岛素峰值后移的关系,并分析不同基因型对胰岛素功能的影响。方法 选取2022 年1 月~ 2023 年1 月在佛山市南海区妇幼保健院就诊的PCOS 患者191 例,同时进行MTHFR基因C677T 位点、胰岛素释放试验(insulin release test,IRT)和空腹血糖(fasting plasma glucose,FPG)检测。根据IRT 峰值所在的时间点进行分组,峰值在120 或者180min 的患者纳入后移组(n=65),在30 或者60min 的纳入无后移组(n=126), 比较两组基因型分布和等位基因频率的差异;分析组内不同基因型对FPG, IRT 各时间点血清胰岛素水平、胰岛素抵抗指数(insulin resistance index,IRI) 、胰岛素敏感指数(insulin sensitivity index,ISI) 和胰岛素曲线下面积(area under the curve,AUC)的影响。结果 ①后移组和无后移组MTHFR C677T 三种基因型(CC,CT,TT)的分布为36.92%,40.00%,23.08% 和61.11%,30.16%,8.73%;等位基因(C,T) 的频率为56.92%, 43.08% 和76.19%,23.81%, 差异均有统计学意义(χ2=12.47,15.06;P=0.020,0.000)。②单因素方差分析显示,无后移组三种基因型的空腹胰岛素(fasting insulin ,Fins)和IRI 差异有统计学意义(F=6.569,5.928,P=0.002,0.003);CT 型、TT 型均高于CC 型[Fins:12.56(9.39,15.49),12.59(9.56,22.48) vs 8.75(5.43,13.50);IRI: 2.75(1.96,3.53),3.16(2.01,4.83) vs1.87(1.28,3.03)],差异均有统计学意义(t=2.66 ~ 2.93, P=0.004 ~ 0.009)。③后移组三种基因型单因素方差分析显示,Fins 和ISI 差异有统计学意义(F=3.827,3.559,P=0.027,0.034),相比于CC 型,CT 型和TT 型的Fins 升高[13.00(9.29,20.74),13.92(7.84,18.03) vs 8.67(6.73,10.66)],而ISI 降低[0.016(0.010,0.023),0.014(0.011,0.025) vs 0.022(0.018,0.033)], 差异均有统计学意义(t=2.11 ~ 2.51, P=0.015 ~ 0.039)。结论 PCOS 患者MTHFR C677T 基因位点多态性与胰岛素峰值后移有关,基因突变患者Fins 升高。在未发生峰值后移的患者中,基因突变者抵抗程度增加;而在峰值后移的患者中,基因突变者胰岛素敏感性降低。
Abstract:
Objective To investigate the relationship between C677T polymorphism of methylene tetrahydrofolate reductase(MTHFR) and peak shift of insulin in patients with polycystic ovary syndrome(PCOS),and the insulin function of different genotypes were compared. Methods A total of 191 women with PCOS were recruited from January 2022 to January 2023 at Nanhai District Maternal and Child Health Hospital in Foshan. The polymorphism of MTHFR gene C677T,insulin release test(IRT) and fasting plasma glucose(FPG) were measured.According to the peak time of IRT,the patients were divided into peakshift group(n=65) at 120 or 180min and non-peak-shift group (n=126) at 30 or 60min,differences of genotype distribution and allele frequency between the two groups were analyzed. Comparing FPG,serum insulin level at each time point of IRT, insulin resistance index(IRI), Insulin sensitivity index(ISI) and area under the curve(AUC) between different genotypes in the two groups. Results ① The frequencies of three MTHFR C677T genotypes(CC,CT,TT) in peak-shift group and non-peak-shift group were 36.92%, 40.00%, 23.08% and 61.11%, 30.16%, 8.73%, and the distribution frequency of C and T were 56.92%, 43.08% and 76.19%, 23.81%, and the differences were statistically significant (χ2=12.47, 15.06, P=0.020, 0.000). ② One-way ANOVA showed that there were significant differences in fasting insulin (Fins) and IRI among the three genotypes in the non-post shift group(F=6.569, 5.928, P=0.002, 0.003). Fins and IRI of CT and TT genotype were higher than those of CC genotype[Fins: 12.56(9.39, 15.49), 12.59(9.56, 22.48) vs 8.75(5.43, 13.50);IRI: 2.75(1.96, 3.53), 3.16(2.01, 4.83) vs 1.87(1.28, 3.03)], and the differences were statistically significant(t=2.66 ~ 2.93, P=0.004 ~ 0.009). ③ Fins and ISI were significantly different among the three genotypes(F=3.827, 3.559, P=0.027, 0.034).Compared with CC genotype, Fins of CT genotype and TT genotype increased[13.00(9.29, 20.74), 13.92(7.84, 18.03) vs 8.67(6.73, 10.66)],while ISI decreased[0.016(0.010, 0.023), 0.014(0.011, 0.025)vs 0.022(0.018, 0.033)], the differences were statistically significant(t=2.11 ~ 2.51, P=0.015 ~ 0.039). Conclusion The polymorphism of MTHFR C677T gene was associated with insulin peak shift in patients with PCOS and Fins was increased in the patients with MTHFR C677T gene mutation.In the patients with no peak insulin shift,the resistance was increased in the patients with the mutation. While in the patients with the peak insulin shift, the insulin sensitivity was decreased.

参考文献/References:

[1] 曾宇, 赵琳. 多囊卵巢综合征糖、脂代谢异常的研究进展[J]. 大连医科大学学报, 2022, 44(3): 263-268. ZENG Yu, ZHAO Lin. Research progress of glucose and lipid metabolic abnormalities in polycystic ovary syndrome[J]. Journal of Dalian Medical University,2022, 44(3): 263-268.
[2] 吴星萍. 多囊卵巢综合征患者并发症与妊娠结局的关系[J]. 实用妇科内分泌电子杂志, 2021, 8(23): 67-69. WU Xingping. Relationship between complications and pregnancy outcomes in patients with polycystic ovary syndrome[J]. Electronic Journal of Practical Gynecological Endocrinology, 2021, 8(23): 67-69.
[3] TAKAHASHI K, NAKAMURA H, SATO H, et al. Four plasma glucose and insulin responses to a 75 g OGTT in healthy young Japanese Women [J]. Journal of Diabetes Research, 2018, 2018: 5742497.
[4] 傅晓华, 朱晶, 张岭, 等. “瘦型”多囊卵巢综合征患者骨骼肌间脂肪与胰岛素抵抗关系的研究[J]. 浙江医学, 2019, 41(6): 571-574. FU Xiaohua, ZHU Jing, ZHANG Ling, et al. The relationship of intermuscular adipose tissue with insulin resistance in ‘thin type’ PCOS patients [J]. Zhejiang Medical Journal, 2019, 41(6): 571-574.
[5] 刘倩文, 周国强, 叶柱均, 等. MTHFR 基因多态性和脂蛋白磷脂酶A2 在糖尿病周围血管病变中的分析[J]. 实验与检验医学, 2022, 40(2): 171-174. LIU Qianwen, ZHOU Guoqiang, YE Zhujun, et al. Analysis of MTHFR gene polymorphism and lipoprotein phospholipase A2 in diabetic peripheral vascular disease LIU[J]. Experimental and Laboratory Medicine, 2022, 40(2): 171-174.
[6] 王佳美, 钱美琪, 魏军, 等. 利用GEO 数据库分析糖尿病患者冠心病易感相关基因表达差异的生物信息学分析[J]. 中国急救复苏与灾害医学杂志, 2023,18(1): 12-17, 26. WANG Jiamei, QIAN Meiqi, WEI Jun, et al. Bioinformatics analysis of gene expression differences in susceptibility to coronary heart disease in diabetic patients using GEO database[J]. China Journal of Emergency Resuscitation and Disaster Medicine, 2023,18(1): 12-17, 26.
[7] 倪菲菲, 郑加永, 徐晓敏, 等. 血清同型半胱氨酸、叶酸、维生素B12 水平及MTHFR 基因C677T 多态性与妊娠期糖尿病的相关性研究[J]. 中国现代医生,2020, 58(12): 68-71. NI Feifei, ZHENG Jiayong, XU Xiaomin, et al. Correlation between serum homocysteine, folic acid,vitamin B12 and MTHFR gene C677T polymorphism and gestational diabetes mellitus[J]. China Modern Doctor, 2020, 58(12): 68-71.
[8] 中华医学会妇产科学分会内分泌学组及指南专家组. 多囊卵巢综合征中国诊疗指南[J]. 中华妇产科杂志, 2018,53 (1): 2-6. Endocrinology Subgroup and Expert Panel, Chinese Society of Obstetrics and Gyneocology, Chinese Medical Association. Chinese guideline for diagnosis and management of polycystic ovary syndrome[J]. Chinese Journal of Obstetrics and Gynecology,2018,53(1):2-6
[9] 徐将, 祝捷, 杨光伟, 等. 初诊断2 型糖尿病患者糖化血红蛋白水平与胰岛α 细胞及β 细胞功能的相关性[J]. 中国临床保健杂志, 2020, 23(4): 487-490. XU Jiang, ZHU Jie, YANG Guangwei, et al. Relationship between different HbA1c levels and islet α-cell and β-cell function in newly diagnosed patients with type 2 diabetes mellitus[J]. Chinese Journal of Clinical Healthcare, 2020, 23(4): 487-490.
[10] 乔晓玲, 郗光霞. 遗传学因素对2 型糖尿病第一时相胰岛素分泌的影响[J]. 国际内分泌代谢杂志,2021, 41(3): 216-219. QIAO Xiaoling, XI Guangxia. Effect of genetic factors on first-phase insulin secretion in patients with type 2 diabetes mellitus[J]. International Journal of Endocrinology and Metabolism, 2021, 41(3): 216-219.
[11] 史琳涛, 李丽君, 程玉霞, 等. 正常体重女性胰岛素早时相分泌受损与妊娠期糖尿病发病关系研究[J].中国糖尿病杂志, 2022, 30(6): 416-420. SHI Lintao, LI Lijun, CHENG Yuxia, et al. The relationship between impaired insulin secretion in early phase and gestational diabetes mellitus in normal weight mothers[J]. Chinese Journal of Diabetes, 2022,30(6): 416-420.
[12] SUN Yun, HAN Junfeng, LIN Ziwei, et al. Delayed insulin secretion response during an OGTT is associated with an increased risk for incidence of diabetes in NGT subjects[J]. Journal of Diabetes and Its Complications,2016, 30(8): 1537-1543.
[13] 王玲玲, 郭志国, 陶晓明, 等. 亚甲基四氢叶酸还原酶基因多态性及甲状腺功能与妊娠期糖尿病的相关性[J]. 中国实验诊断学, 2021, 25(6): 825-829. WANG Lingling, GUO Zhiguo, TAO Xiaoming, et al. Association of methylene tetrahydrofolate reductase gene polymorphism and thyroid function indicators with gestational diabetes mellitus[J]. Chinese Journal of Laboratory Diagnosis, 2021, 25(6): 825-829.
[14] 张萍萍, 张小平. 血清AMH, visfatin, irisin 水平变化与多囊卵巢综合征患者HOMA-IR 指数的关联性及临床意义探讨[J]. 中国实验诊断学, 2018, 22(1): 73-74. ZHANG Pingping, ZHANG Xiaoping. Correlation and clinical significance of serum AMH, visfatin and irisin levels with HOMA-IR index in patients with polycystic ovary syndrome [J]. Chinese Journal of Laboratory Diagnosis, 2018, 22(1): 73-74.
[15] 郭丽娟, 葛双雷, 许慧, 等. 微量元素与PCOS 患者内分泌代谢、胰岛素抵抗相关性研究[J]. 中国实验诊断学, 2022, 26(7): 1042-1044. GUO Lijuan, GE Shuanglei, XU Hui, et al. Study on correlation between trace elements and endocrine metabolism and insulin resistance in PCOS patients [J].Chinese Journal of Laboratory Diagnosis, 2022, 26(7):1042-1044.
[16] 方建红, 张淑红, 徐敏, 等. MTHFR 基因多态性与血清叶酸水平对妊娠期糖尿病患者及其妊娠结局的影响[J]. 中华妇幼临床医学杂志( 电子版), 2021,17(3): 291-297. FANG Jianhong, ZHANG Shuhong, XU Min, et al. Effects of MTHFR gene polymorphism and serum folic acid level on pregnant women with gestational diabetes mellitus and their pregnancy outcomes [J].Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2021, 17(3): 291-297.
[17] 张燕, 王伟红, 郝万鹏. 乌鲁木齐汉族妇女亚甲基四氢叶酸还原酶基因变异与血清叶酸和同型半胱氨酸水平的相关性研究[J]. 现代检验医学杂志, 2019,34(5): 98-100, 105. ZHANG Yan, WANG Weihong, HAO Wanpeng. Study on the correlation between the variation of methylenetetrahydrofolate reductase gene and folate and homocysteine in Urumqi han women [J]. Journal of Modern Laboratory Medicine, 2019, 34(5): 98-100, 105.
[18] 邹卓群, 刘梅, 孙可可, 等. 体检人群同型半胱氨酸水平与心血管疾病的关系[J]. 河北医药, 2018,40(13): 2050-2053, 2057. ZOU Zhuoqun, LIU Mei, SUN Keke, et al. Correlation between homocysteine levels and cardiovascular diseases in physical examination population[J]. Hebei Medical Journal, 2018, 40(13): 2050-2053, 2057.
[19] 谷雨明, 黄延芹, 徐云生. 不同糖调节状态胰岛素双相分泌的研究进展[J]. 东南大学学报( 医学版), 2016,35(4): 640-642. GU Yuming, HUANG Yanqin, XU Yunsheng. Research progress of biphasic insulin secretion in different glucose regulated states [J]. Journal of Southeast University(Medical Science Edition), 2016, 35(4): 640-642.
[20] KAO K T, SABIN M A. Type 2 diabetes mellitus in children and adolescents[J]. Australian Family Physician, 2016, 45(6): 401-406.
[21] 贺星星, 马晓静, 应令雯, 等. 新诊断标准下糖尿病前期人群胰岛β 细胞功能和胰岛素敏感性的特点分析[J]. 上海交通大学学报( 医学版), 2018, 38(8):940-947. HE Xingxing, MA Xiaojing, YING Lingwen, et al. Characteristic analysis of insulin secretion and sensitivity in pre-diabetes populations under new diagnostic criteria[J]. Journal of Shanghai Jiaotong University(Medical Science), 2018, 38(8): 940-947.
[22] 朱琳, 林延润, 杨发达, 等. PCOS 患者胰岛素释放试验峰值后移与胰岛素分泌总量及敏感性的特征分析[J]. 现代检验医学杂志, 2022, 37(5): 154-158. ZHU Lin, LIN Yanrun, YANG Fada, et al. Analysis of the relationship between the peak shift of insulin release test and total insulin secretion and sensitivity in patients with PCOS[J]. Journal of Modern Laboratory Medicine, 2022, 37(5): 154-158.
[23] 田思敏, 唐明敏, 刘洋, 等. 2 型糖尿病胰岛素抵抗发生机制的研究进展[J]. 新疆医科大学学报, 2015,38(10): 1317-1320. TIAN Simin, TANG Mingmin, LIU Yang, et al. Advances in the pathogenesis of insulin resistance in type 2 diabetes mellitus [J]. Journal of Xinjiang Medical University, 2015, 38(10): 1317-1320.

相似文献/References:

[1]曹云,周晓,张晓艳,等.陕西省延安地区育龄女性MTHFR基因多态性和国内多地区相关报道比较分析2)[J].现代检验医学杂志,2019,34(01):62.[doi:10.3969/j.issn.1671-7414.2019.01.016]
 CAO Yun,ZHOU Xiao,ZHANG Xiao-yan,et al.Comparative Analysis of MTHFR Gene Polymorphisms in Women of Childbearing Age in Yan’an Area of Shaanxi Province and Related Reports in Many Regions in China[J].Journal of Modern Laboratory Medicine,2019,34(06):62.[doi:10.3969/j.issn.1671-7414.2019.01.016]
[2]李雅静,张 瑞,吴 欣,等.H型高血压并发缺血性脑卒中患者MTHFR C677T基因多态性及血清Hcy水平的相关性研究[J].现代检验医学杂志,2019,34(02):9.[doi:10.3969/j.issn.1671-7414.2019.02.003]
 LI Ya-jing,ZHANG Rui,WU Xin,et al.Relationship between MTHFR C677T Gene Polymorphismsand Serum Hcy Level in H Type Hypertension with Ischemic Stroke[J].Journal of Modern Laboratory Medicine,2019,34(06):9.[doi:10.3969/j.issn.1671-7414.2019.02.003]
[3]张 燕,王伟红,郝万鹏.乌鲁木齐汉族妇女亚甲基四氢叶酸还原酶基因变异与血清叶酸和同型半胱氨酸水平的相关性研究[J].现代检验医学杂志,2019,34(05):98.[doi:10.3969/j.issn.1671-7414.2019.05.024]
 ZHANG Yan,WANG Wei-hong,HAO Wan-peng.Study on the Correlation between the Variation of Methylenetetrahydrofolate Reductase Gene and Folate and Homocysteine in Urumqi Han Women[J].Journal of Modern Laboratory Medicine,2019,34(06):98.[doi:10.3969/j.issn.1671-7414.2019.05.024]
[4]师文涛,白 蓉,黄剑林,等.陕西省延安地区汉族与国内其他地区育龄妇女 MTHFR 基因 C677T 位点基因型和等位基因分布研究[J].现代检验医学杂志,2020,35(06):78.[doi:doi:10.3969/j.issn.1671-7414.2020.06.019]
 SHI Wen-tao,BAI Rong,HUANG Jian-lin,et al.Comparative Study on MTHFR Gene C677T Locus Genotype and AlleleDistribution between Han Nationality and Women of ChildbearingAge in Yan’an Area of Shaanxi Province[J].Journal of Modern Laboratory Medicine,2020,35(06):78.[doi:doi:10.3969/j.issn.1671-7414.2020.06.019]
[5]李晓丽,赵 莉,曹阳阳,等.多囊卵巢综合征患者血清肌联素水平表达与多种生化代谢指标的相关性分析[J].现代检验医学杂志,2020,35(06):111.[doi:doi:10.3969/j.issn.1671-7414.2020.06.027]
 LI Xiao-li,ZHAO Li,CAO Yang-yang,et al.Correlation Analysis between Expression of Serum Myonectin and VariousBiochemical and Metabolic Indexes in Patients with Polycystic Ovary Syndrome[J].Journal of Modern Laboratory Medicine,2020,35(06):111.[doi:doi:10.3969/j.issn.1671-7414.2020.06.027]
[6]傅金瑞,唐淑稳.育龄妇女亚甲基四氢叶酸还原酶~MTHFR基因C677T,A1298C位点多态性与HR-HPV感染的相关性研究[J].现代检验医学杂志,2021,36(02):53.[doi:doi:10.3969/j.issn.1671-7414.2021.02.013]
 FU Jin-rui,TANG Shu-wen.Study of the Relationship between MTHFR~C677T,A1298CPolymorphism and HR-HPV Infection in Women of Childbearing Age[J].Journal of Modern Laboratory Medicine,2021,36(06):53.[doi:doi:10.3969/j.issn.1671-7414.2021.02.013]
[7]钟社兰,李功娟,樊阳阳,等.多囊卵巢综合征患者血清中Neudesin水平及其与多项生理生化指标的相关性分析[J].现代检验医学杂志,2021,36(02):98.[doi:doi:10.3969/j.issn.1671-7414.2021.02.023]
 ZHONG She-lan,LI Gong-juan,FAN Yang-yang,et al.Correlation Analysis of Serum Neudesin Level and Multiple Physiological and Biochemical Indexes in Patients with Polycystic Ovarian Syndrome[J].Journal of Modern Laboratory Medicine,2021,36(06):98.[doi:doi:10.3969/j.issn.1671-7414.2021.02.023]
[8]曹阳阳,樊阳阳,宋秀英,等.多囊卵巢综合征患者血清镍纹样蛋白水平检测的临床意义及与实验室指标的相关性研究[J].现代检验医学杂志,2021,36(02):111.[doi:doi:10.3969/j.issn.1671-7414.2021.02.026]
 CAO Yang-yang,FAN Yang-yang,SONG Xiu-ying,et al.Clinical Significance of Serum Metrnl Protein Level Detection in Patients with Polycystic Ovary Syndrome and Its Correlation with Laboratory Indexes[J].Journal of Modern Laboratory Medicine,2021,36(06):111.[doi:doi:10.3969/j.issn.1671-7414.2021.02.026]
[9]宋秀英,樊阳阳,赵 莉,等.多囊卵巢综合征患者血清 Spexin 水平表达及其与多项生理生化指标的相关性分析[J].现代检验医学杂志,2021,36(03):80.[doi:10.3969/j.issn.1671-7414.2021.03.018]
 SONG Xiu-ying,ZHAO Li,CAO Yang-yang,et al.Expression of Serum Spexin in Patients with Polycystic Ovary Syndrome andIts Correlation with Multiple Physiological and Biochemical Indexes[J].Journal of Modern Laboratory Medicine,2021,36(06):80.[doi:10.3969/j.issn.1671-7414.2021.03.018]
[10]林延润a,邱伟全b,彭学博,等.多囊卵巢综合征患者血清性激素水平与胰岛素释放峰值后移的相关性研究[J].现代检验医学杂志,2021,36(06):143.[doi:10.3969/j.issn.1671-7414.2021.06.031]
 LIN Yan-run,PENG Xue-bo,QIU Wei-quan,et al.Study on the Relationship between Serum Sex Hormone Level and Insulin Release Peak Shift in Patients with Polycystic Ovary Syndrome[J].Journal of Modern Laboratory Medicine,2021,36(06):143.[doi:10.3969/j.issn.1671-7414.2021.06.031]

备注/Memo

备注/Memo:
基金项目: 佛山市自筹经费类科技创新项目入库培育项目(编号:2220001004289):PCOS 患者胰岛素峰值后移与MTHFRC677T 基因多态性的相关性研究。
作者简介:朱琳(1985-),女,本科,副主任技师,研究方向:产前筛查与产前诊断方向,E-mail: 422207430@qq.com。
更新日期/Last Update: 2023-11-15