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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
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  • 收稿日期:  2023-02-24
  • 网络出版日期:  2023-06-16
  • 刊出日期:  2023-06-25

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