留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

DDAH1基因836A/T多态性与云南地区汉族2型糖尿病肾脏疾病的相关性分析

谭洪 殷和佳 李妍 胡琴 李斓 任遵丹 石柔

谭洪, 殷和佳, 李妍, 胡琴, 李斓, 任遵丹, 石柔. DDAH1基因836A/T多态性与云南地区汉族2型糖尿病肾脏疾病的相关性分析[J]. 昆明医科大学学报, 2023, 44(6): 26-32. doi: 10.12259/j.issn.2095-610X.S20230621
引用本文: 谭洪, 殷和佳, 李妍, 胡琴, 李斓, 任遵丹, 石柔. DDAH1基因836A/T多态性与云南地区汉族2型糖尿病肾脏疾病的相关性分析[J]. 昆明医科大学学报, 2023, 44(6): 26-32. doi: 10.12259/j.issn.2095-610X.S20230621
Hong TAN, Hejia YIN, Yan LI, Qin HU, Lan LI, Zundan REN, Rou SHI. Correlation between DDAH1 Gene 836A/T Polymorphism and Type 2 Diabetic Kidney Disease in Yunnan Han Population[J]. Journal of Kunming Medical University, 2023, 44(6): 26-32. doi: 10.12259/j.issn.2095-610X.S20230621
Citation: Hong TAN, Hejia YIN, Yan LI, Qin HU, Lan LI, Zundan REN, Rou SHI. Correlation between DDAH1 Gene 836A/T Polymorphism and Type 2 Diabetic Kidney Disease in Yunnan Han Population[J]. Journal of Kunming Medical University, 2023, 44(6): 26-32. doi: 10.12259/j.issn.2095-610X.S20230621

DDAH1基因836A/T多态性与云南地区汉族2型糖尿病肾脏疾病的相关性分析

doi: 10.12259/j.issn.2095-610X.S20230621
基金项目: 云南省科技厅科技计划昆明医科大学联合专项基金资助项目(202001AY070001-034);云南省高层次卫生计生技术人才培养经费资助项目 (D-2019011);云南省代谢性疾病临床医学研究中心项目(202102AA100056);昆明医科大学科技创新团队 ( CXTD202101)
详细信息
    作者简介:

    谭洪(1973~),男,云南文山人,学士,副主任医师,主要从事糖尿病及其并发症临床研究

    通讯作者:

    石柔,E-mail:shirourou325@sian.com

  • 中图分类号: R587.1

Correlation between DDAH1 Gene 836A/T Polymorphism and Type 2 Diabetic Kidney Disease in Yunnan Han Population

  • 摘要:   目的  探讨DDAH1基因836A/T多态性与云南地区汉族人群2型糖尿病肾脏疾病发生的相关性。  方法  选取T2DM患者共660例,根据UACR检测结果,将患者分为3组:单纯2型糖尿病组(DN0组),合并早期肾病组(DN1组),合并临床期肾病组(DN2组)。 健康人群(NC组)304例。采用PCR-DNA测序技术对DDAH1基因836A/T多态性进行基因分型,ELISA 法检测血浆非对称性二甲基精氨酸(ADMA)浓度。  结果  DDAH1基因836位点AA基因型在DN1 + DN2组的分布频率高于DN0组 (P < 0.05)。A等位基因在DN1 + DN2组的分布频率高于DN0组 (P < 0.05)。T2DM患者中AA基因型携带者较AT+TT基因型个体具有更高的ADMA水平。ADMA水平在DN1 + DN2组高于DN0组(P < 0.05)。通过相关危险因素分析发现, 在T2DM患者中ADMA水平、DDAH1基因836位点AA基因型是发生DKD的危险因素。  结论  DDAH1基因836位点AA基因型可能是云南地区汉族T2DM 患者发生DKD的危险因素,AA基因型携带者ADMA水平升高。
  • 图  1  DDAH1基因836AA基因型对应的测序图

    Figure  1.  DDAH1 gene 836AA genotype sequencing

    图  2  DDAH1基因836TT基因型对应的测序图

    Figure  2.  DDAH1 gene 836TT genotype sequencing

    图  3  DDAH1基因836AT基因型对应的测序图

    Figure  3.  DDAH1 gene 836AT genotype sequencing

    表  1  PCR引物序列

    Table  1.   PCR primer sequences

    基因多态性位点上游引物序列下游引物序列
    DDAH1基因836A/T5′- TGGTCTCCTCTGCCTCTGAC -3′5′-GGTGATCGCTTCCTGAACAT-3′
    下载: 导出CSV

    表  2  各组间临床资料比较($\bar x \pm s $

    Table  2.   Comparison of clinical data of each group ($\bar x \pm s $

    指标NCDN0DN1DN2DN1+DN2FP
    年龄(岁) 54.62 ± 10.58 54.64 ± 10.73 55.75 ± 10.42 57.28 ± 11.67 56.36 ± 11.36 2.758 0.13
    病程(月) 72.13 ± 25.09 92.23 ± 43.62 109.18 ± 45.69△▲ 100.24 ± 51.46△▲ 9.364 < 0.001
    收缩压(mmHg) 117.59 ± 13.26 122.64 ± 16.72 133.52 ± 18.54*△ 142.65 ± 21.17*△#▲ 138.83 ± 19.82*△ 11.5 < 0.001
    舒张压(mmHg) 77.15 ± 7.63 78.25 ± 10.02 82.42 ± 11.54 81.76 ± 12.22 82.05 ± 12.09 0.831 0.598
    血肌酐(mmol/L) 63.2 ± 18.55 65.7 ± 18.25 69.43 ± 19.43* 79.17 ± 24.64*△# 73.76 ± 26.78* 15.684 < 0.001
    尿酸(mmol/L) 337.36 ± 87.62 337.89 ± 86.72 335.58 ± 104.05 354.32 ± 102.91*△# 346.62 ± 103.42 7.275 < 0.001
    TC(mmol/L) 4.39 ± 1.07 4.38 ± 1.25 4.51 ± 1.34 4.43 ± 1.27 4.49 ± 1.33 1.26 0.289
    TG (mmol/L) 1.25 ± 0.98 2.63 ± 1.42* 2.67 ± 1.78* 2.31 ± 1.45* 2.52 ± 1.79* 10.24 < 0.001
    HLD(mmol/L) 1.29 ± 0.34 1.03 ± 0.35 1.01 ± 0.29 0.98 ± 0.75 1.00 ± 0.31 0.75 0.52
    LDL (mmol/L) 2.52 ± 1.22 2.58 ± 1.52 2.83 ± 2.14*△ 2.79 ± 1.86*△ 2.82 ± 1.75*△ 5.19 0.002
    HbA1C (%) 6.17 ± 2.25 8.50 ± 2.12* 8.57 ± 2.06* 8.66 ± 2.63* 8.61 ± 2.05* 11.04 < 0.001
    ADMA (μmol/L) 0.62 ± 0.23 1.06 ± 0.27* 1.23 ± 0.42*△ 1.29 ± 0.53*△ 1.27 ± 0.41*△▲ 12.424 < 0.001
      与NC组比较,* P < 0.05;与DN0组比较,P < 0.05;与DN1组比较,#P < 0.05;协方差分析,P < 0.05。
    下载: 导出CSV

    表  3  各组间基因型频率和等位基因频率[n(%)](1)

    Table  3.   The genotype and allele frequencies in each group [n(%)](1)

    组别n基因型χ2P
    AAAT+TT
    NC组 304 128(42.1) 176(57.9) 11.863 0.013
    DN0组 296 146(49.6)* 150(50.4)
    DN1组 190 112(58.9)* 78(41.1)
    DN2组 174 98(56.3)*# 76(43.7)
    DN1+DN2组 364 210(57.7)*# 154(42.3)
      与NC组比较,*P < 0.05;与DN0组比较,#P < 0.05。
    下载: 导出CSV

    表  3  各组间基因型频率和等位基因频率[n(%)](2)

    Table  3.   The genotype and allele frequencies in each group [n(%)](2)

    组别n等位基因χ2P
    AT
    NC组 304 398 (65.5) 210(34.5) 19.318 0.001
    DN0组 296 416(70.3)* 176(29.7)
    DN1组 190 290(76.3)* 90(23.7)
    DN2组 174 262(75.3)*# 86(24.7)
    DN1+DN2组 364 552(75.8)*# 176(24.2)
      与NC组比较,*P < 0.05;与DN0组比较,#P < 0.05。
    下载: 导出CSV

    表  4  T2DM患者中不同基因型间临床资料比较($\bar x \pm s $)(1)

    Table  4.   Comparison of clinical data of DDAH1 genotype of T2DM patients ($\bar x \pm s $)(1)

    基因型收缩压(mmHg)舒张压(mmHg)血肌酐(mmol/L)尿酸(mmol/L)TC(mmol/L)
    AA 130.26 ± 17.43 79.53 ± 9.76 74.62 ± 23.64 344.41 ± 103.42 4.48 ± 1.04
    AT+TT 129.82 ± 17.84 78.05 ± 10.62 72.58 ± 21.93 338.51 ± 91.45 4.38 ± 126
    下载: 导出CSV

    表  4  T2DM患者中不同基因型间临床资料比较($\bar x \pm s $)(2)

    Table  4.   Comparison of clinical data of DDAH1 genotype of T2DM patients ($\bar x \pm s $)(2)

    基因型收缩压(mmHg)舒张压(mmHg)血肌酐(mmol/L)尿酸(mmol/L)TC(mmol/L)
    AA 2.50 ± 1.42 1.06 ± 0.27 2.92 ± 1.68 9.12 ± 2.21 1.39 ± 0.34
    AT+TT 2.57 ± 1.82 1.01 ± 0.33 2.85 ± 1.74 8.71 ± 2.08 1.09 ± 0.27 *
      2组间比较,*P < 0.05。
    下载: 导出CSV

    表  5  T2DM-DKD发生的危险因素的Logistic分析

    Table  5.   Logistic regression analysis of T2DM-DKD occurence

    进入回归方程的变量BS.E.WaldPOROR值的95%CI
    下限上限
    病程(月)) 0.821 0.476 5.365 0.021 1.103 1.152 3.275
    ADMA(μmol/L) 1.374 0.602 5.473 0.029 3.973 1.228 10.876
    AA基因型 1.538 0.452 10.384 0.001 4.421 1.734 9.326
    下载: 导出CSV

    表  6  T2DM-DKD发展的危险因素的Logistic分析

    Table  6.   Logistic regression analysis of T2DM-DKD development

    进入回归方程的变量BS.E.WaldPOROR值的95%CI
    下限上限
    病程(月)0.8620.368 11.1780.0012.4101.4764.632
    SBP(mmHg)1.4230.5746.6920.0234.3351.431 12.795
    下载: 导出CSV
  • [1] American Diabetes Association Professional Practice Committee. Classification and diagnosis of diabetes: Standards of medical care in diabetes-2022. Amer diabet assoc professional pra jan 2022[J]. Diabetes Care,2022,45(9):S17-S38.
    [2] Alhaider A A,Korashy H M,Sayed-Ahmed M M,et al. Metformin attenuates streptozotocin-induced diabetic nephropathy in rats through modulation of oxidative stress genes expression[J]. Chem Biol Interact,2011,192(3):233-242. doi: 10.1016/j.cbi.2011.03.014
    [3] Michael D W,Ting G,Kristen S,et al. Enhancing kidney DDAH-1 expression by adenovirus delivery reduces ADMA and ameliorates diabetic nephropathy[J]. America Journal Of Physiology-Renal Physiology,2020,318(2):509-517. doi: 10.1152/ajprenal.00518.2019
    [4] Mannino G C,Pezzilli S,Averta C,et al. A functional variant of the dimethylarginine dimethylaminohydrolase-2 gene is associated with myocardial infarction in type 2 diabetic patients[J]. Cardiovasc Diabetol.,2019,18(1):102. doi: 10.1186/s12933-019-0906-1
    [5] Rhys D. Fogarty,Sotoodeh Abhary,Shahrbanou Javadiyan,et al. Rlationship between DDAH gene variants and serum a ADMA level in individuals with type 1 diabetes[J]. Diabetes Complications,2012,26(3):195-198. doi: 10.1016/j.jdiacomp.2012.03.022
    [6] 中华医学会糖尿病学分会. 中国2型糖尿病防治指南(2017年版)[J]. 中华糖尿病杂志,2018,10(1):4-67. doi: 10.3760/cma.j.issn.1674-5809.2018.01.003
    [7] 石柔,张娴,谭洪,等. 云南地区汉族2型糖尿病患者二甲基精氨酸二甲胺水解酶1、二甲基精氨酸二甲胺水解酶2基因单核苷酸多态性与动脉粥样硬化关系的研究[J]. 中国糖尿病杂志,2021,29(5):321-327. doi: 10.3969/j.issn.1006-6187.2021.05.001
    [8] Dagar N,Das P,Bisht P,et al. Diabetic nephropathy: A twisted thread to unravel[J]. Life Sciences,2021,278(8):119635.
    [9] Creager M A,Luscher T F,Cosentino F,et al. Diabetes and vascular disease: pathophysiology,clinical consequences,and medical therapy: Part I[J]. Circulation,2003,108(12):1527-1532. doi: 10.1161/01.CIR.0000091257.27563.32
    [10] Wieczor R,Wieczor A M,Rosc D J,et al. ADMA (asymmetric dimethylarginine) and angiogenic potential in patients with type 2 diabetes and prediabetes[J]. Experimental Biology and Medicine,2020,246(2):153-162.
    [11] Mihout F,Shweke N,N Big´e,et al. Asymmetric dimethylarginine(ADMA) induces chronic kidney disease through a mechanism involving collagen and TGF-β1 synthesis[J]. The Journal of Pathology,2011,223(1):37-45. doi: 10.1002/path.2769
    [12] Mei Rong D,Gui Xia J,Nian Sheng L,et al. Role of Asymmetrical Dimethyl- arginine in Diabetic Microvascular Complications[J]. Journal of Cardiovascular Pharmacology,2016,68(4):322-326. doi: 10.1097/FJC.0000000000000414
    [13] Jing L,Caiying L,Wen C,et al. Relationship between serum asymmetric dimethylarginine level and microvascular complications in diabetes mellitus:A meta-analysis[J]. BioMed Research International,2019,2019:2941861.
    [14] Isaivani J,Saravanakumar S,Prabu P,et al. Association of circulatory asymmetric dimethylarginine (ADMA) with diabetic nephropathy in Asian Indians and its causative role in renal cell injury[J]. Clinical Biochemistry,2017,50(15):835-842. doi: 10.1016/j.clinbiochem.2017.05.007
    [15] Hu X,Atzler D,Xu X,et al. Dimethylarginine dimethylaminoh ydrolase-1 is the critical enzyme for degrading the cardiovascular risk factor asymmetrical dimethylarginine[J]. Arterioscler Thromb Vasc Biol,2011,31(1):1540-1546.
    [16] Roman N R,Natalia J,Alfred S,et al. ADMA elevation does not exacerbate development of diabetic nephropathy in mice with streptozotocin-induced diabetes mellitus[J]. Atherosclerosis Supplements,2019,30:319-325.
    [17] Shi L L,Zhao C Y,Wang H Y,et al. Dimethylarginine dimethylamin ohydrolase 1 deficiency induces the epithelial to mesenchymal transition in renal proximal tubular epithelial cells and exacerbates kidney damage in aged and diabetic mice[J]. Antioxidants & Redox Signaling,2017,27(16):1347-1360.
    [18] Abhary S,Burdon K P,Kuot A,et al. Sequence variation in DDAH1 and DDAH2 genes is strongly and additively associated with serum ADMA concentrations in individuals with Type 2 diabetes[J]. Plos One,2010,5(3):e9462. doi: 10.1371/journal.pone.0009462
    [19] Lind L,Ingelsson E,Kumar J,et al. Genetic variation in the dimethylarginine dimethylaminohydrolase 1 gene (DDAH1) is related to asymmetric dimethylarginine (ADMA) levels,but not to endothelium-dependent vasodilation[J]. Vascular Medicine,2013,18(4):192-199. doi: 10.1177/1358863X13496488
    [20] JHannemann J,Zummack J,Hillig J,et al. Association of variability in the DDAH1,DDAH2,AGXT2 and PRMT1 genes with circulating ADMA concentration in human whole blood[J]. Journal of Clinical Medicine,2022,11(4):941. doi: 10.3390/jcm11040941
    [21] Zhu F S,Zhou C,Wen Z,et al. DDAH1 promoter -396 4N insertion variant is associated with increased risk of type 2 diabetes in a gender‐dependent manner[J]. Molecular Genetics & Genomic Medicine,2020,8(1):e1011.
    [22] Wang S Y,Deng Z X,Zhang H,et al. The effect of haptoglobin genotype on the association of asymmetric dimethylarginine and DDAH 1 polymorphism with diabetic macroangiopathy[J]. Cardiovascular Diabetology,2022,21:265. doi: 10.1186/s12933-022-01702-6
  • [1] 朱新琳, 吴亚楠, 孟琦, 杨千紫, 李元彪, 陶俊衡, 何孟阳.  昆明市2社区2型糖尿病慢病管理患者服药依从性对病情控制的影响, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20240312
    [2] 牛玲, 马蓉, 张程, 苗翠娟, 唐艳, 刘方, 李博一.  2型糖尿病合并骨质疏松患者PTH及ER基因多态性分析, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20240614
    [3] 李博一, 牛玲, 马蓉, 张娴, 刘方, 唐艳, 苗翠娟, 张程, 韩竺君.  护骨素基因启动子区T950C多态性与2型糖尿病合并骨质疏松症的关系, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20220306
    [4] 牛玲, 李博一, 毛静秋, 唐艳, 马蓉, 刘方, 张程, 韩竹君, 苗翠娟, 张娴.  维生素D受体基因多态性与昆明地区2型糖尿病伴骨质疏松症的关系, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20210711
    [5] 李博一, 牛玲, 马蓉, 张娴, 刘方, 唐艳, 苗翠娟, 韩竺君, 张程.  护骨素基因启动子区T950C多态性与昆明地区2型糖尿病伴骨质疏松症的关系, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20211112
    [6] 李博一, 牛玲, 马蓉, 张娴, 刘方, 唐艳, 苗翠娟, 韩竺君, 张程.  降钙素受体基因多态性与昆明地区2型糖尿病伴骨质疏松症的相关性, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20210709
    [7] 姚利璇, 牛奔, 岳伟, 周文林, 张雅婷.  丙型肝炎病毒感染和2型糖尿病的相关性, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20210815
    [8] 梅聪, 翁晓春, 彭葆坤, 颜穗珺, 李春, 周琼, 唐哲.  CLOCK基因rs4580704多态性位点与2型糖尿病和睡眠质量的相关性, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20210332
    [9] 阮愕舒, 王烁, 苏惠, 尹凤琼, 钱忠义, 杨建宇.  人参皂苷Rg1对2型糖尿病大鼠的肾脏保护作用, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20210625
    [10] 陈捷, 郭伟昌, 殷和佳, 严红霞, 张帆, 王尧乙, 李会芳.  RANTES及其受体CCR5基因多态性及环境因素在昆明汉族T2DM发生中的交互作用, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20210606
    [11] 牛玲, 李博一, 张程, 马蓉, 唐艳, 刘方, 尹利民, 韩竺君, 苗翠娟, 张娴.  降钙素受体、维生素D受体基因多态性与昆明地区2型糖尿病合并骨质疏松的关系, 昆明医科大学学报. doi: 10.12259/j.issn.2095-610X.S20211114
    [12] 李佳丽, 周晓伟, 郭伟昌, 陈婕, 张帆, 李会芳.  GAS6基因多态性及其血浆水平与昆明地区汉族糖尿病肾脏疾病的相关性, 昆明医科大学学报.
    [13] 韩文菊, 牛奔, 梁赟, 段晓燕, 苏恒, 薛元明.  甲状腺功能正常的2型糖尿病甲状腺激素与嘌呤代谢和体重的相关性, 昆明医科大学学报.
    [14] 张伟.  ADAM33基因T1、S2位点多态性在中国人支气管哮喘易感性的Meta分析, 昆明医科大学学报.
    [15] 念馨.  金属硫蛋白基因G-201A多态性在2型糖尿病及原发性高血压的分布差异性, 昆明医科大学学报.
    [16] 龙琼华.  2型糖尿病对老年高血压患者颈动脉内膜中层厚度与左心室质量指数的影响及相关性, 昆明医科大学学报.
    [17] 邓德耀.  PGC-1α基因Gly482Ser多态性与2型糖尿病的相关性研究, 昆明医科大学学报.
    [18] 念馨.  2型糖尿病FOXC2基因C-1702T多态性与血清总胆固醇相关性, 昆明医科大学学报.
    [19] 王艳.  ENPP1基因K121Q多态性与2型糖尿病的相关性研究, 昆明医科大学学报.
    [20] 李梅蕊.  PC-1基因多态性与2型糖尿病及糖尿病肾病的相关性研究, 昆明医科大学学报.
  • 加载中
图(3) / 表(8)
计量
  • 文章访问数:  3049
  • HTML全文浏览量:  1805
  • PDF下载量:  9
  • 被引次数: 0
出版历程
  • 收稿日期:  2023-02-24
  • 网络出版日期:  2023-06-16
  • 刊出日期:  2023-06-25

目录

    /

    返回文章
    返回