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ACAT1和MTNR1B基因多态性与非酒精性脂肪性肝病易感性的关系

马磊 胡欣欣 赵波 万强 周林 赵真真 辛永宁

引用本文:
Citation:

ACAT1和MTNR1B基因多态性与非酒精性脂肪性肝病易感性的关系

DOI: 10.12449/JCH240410
基金项目: 

国家自然科学基金 (32171277)

伦理学声明:本研究遵守国家所有相关法规、机构政策和赫尔辛基宣言,并于2017年10月11日经由青岛市市立医院伦理委员会审批,批号:2017临审字第20号(快)。所纳入患者均签署知情同意书。
利益冲突声明:本研究不存在任何利益冲突。
作者贡献声明:马磊、胡欣欣、辛永宁等负责课题设计,资料分析,撰写论文;赵波、万强、周林、赵真真等参与收集数据,修改论文;马磊负责拟定写作思路,指导撰写文章并最后定稿。
详细信息
    通信作者:

    辛永宁, xinyongning@163.com (ORCID: 0000-0002-3692-7655)

Association of polymorphisms of the acetyl-coA acetyltransferase 1 gene and the melatonin receptor 1B gene with the susceptibility to nonalcoholic fatty liver disease

Research funding: 

National Natural Science Foundation of China (32171277)

More Information
  • 摘要:   目的  本研究拟探讨乙酰辅酶A乙酰转移酶1(ACAT1)和褪黑激素受体1B(MTNR1B)基因多态性与非酒精性脂肪性肝病(NAFLD)疾病易感性的关系。  方法  本研究共纳入2020年12月—2022年6月就诊于青岛市市立医院的健康体检者164例、NAFLD患者228例。采用PCR及测序的方法对ACAT1 rs1044925、rs1157651和MTNR1B rs10830963基因多态性进行基因分型,并采集空腹静脉血进行生化检测。符合正态分布的计量资料两组间比较采用成组t检验;非正态分布的计量资料两组间比较采用Mann-Whitney U非参数检验;计数资料两组间比较采用χ2检验。  结果  ACAT1 rs1044925、rs1157651和MTNR1B rs10830963基因型分布在NAFLD及健康对照组间无统计学差异(P值均>0.05),ACAT1 rs1044925 AA基因型携带者的LDL水平明显高于C等位基因携带者(Z=-2.08,P=0.04),MTNR1B rs10830963 G等位基因携带者空腹血糖水平明显高于CC基因型携带者(Z=-3.01,P<0.01)。  结论  ACAT1 rs1044925、rs1157651和MTNR1B rs10830963多态性与NAFLD易感性无明显相关,ACAT1 rs1044925和MTNR1B rs10830963位点分别与LDL和空腹血糖水平有关。

     

  • 表  1  FTO基因引物序列

    Table  1.   Primer sequence of FTO gene

    位点 引物 引物序列(5′-3′)
    rs1044925 primer 1 ACGTTGGATGTGAGCAAATGCAGAAGCCAG
    primer 2 ACGTTGGATGTATTTTGCAGACTAGTGAG
    rs9992651 primer 1 ACGTTGGATGCTCGCAAGAAATAATTCGGG
    primer 2 ACGTTGGATGGAGTAGCTGTTCTCTACTCC
    rs10830963 primer 1 ACGTTGGATGTCCCAGGCAGTTACTGGTTC
    primer 2 ACGTTGGATGTGTCTATGCTGGCAAAGCTG
    下载: 导出CSV

    表  2  两组一般临床资料及相关指标比较

    Table  2.   Comparison of general clinical data and related indicators between NAFLD and control group

    指标 NAFLD组(n=228) 对照组(n=164) 统计值 P
    男/女(例) 120/108 90/74 χ2=0.66 0.68
    年龄(岁) 52(41~63) 39(30~52) Z=-6.50 <0.01
    BMI(kg/m2 27.57±4.67 24.75±3.89 t=-5.25 <0.01
    TBil(μmol/L) 12.50(10.30~16.78) 13.20(10.38~16.50) Z=-0.34 0.73
    ALT(U/L) 28.22(18.00~42.00) 17.59(12.96~26.96) Z=-5.55 <0.01
    AST(U/L) 24.25(19.58~32.89) 20.00(16.07~24.23) Z=-5.20 <0.01
    ALP(U/L) 86.47(72.32~105.99) 74.66(59.60~87.06) Z=-3.60 <0.01
    GGT(U/L) 30.75(22.00~48.92) 18.00(12.00~26.25) Z=-7.16 <0.01
    FPG(mmol/L) 5.12(4.59~6.03) 4.92(4.49~5.22) Z=-2.67 <0.01
    TC(mmol/L) 5.09(4.34~5.81) 4.88(4.27~5.49) Z=-1.57 0.12
    TG(mmol/L) 1.79(1.19~2.49) 1.04(0.79~1.45) Z=-7.33 <0.01
    LDL(mmol/L) 3.15(2.62~3.61) 3.00(2.47~3.45) Z=-1.57 0.12
    HDL(mmol/L) 1.15(1.02~1.32) 1.30(1.13~1.49) Z=-4.08 <0.01
    下载: 导出CSV

    表  3  rs1044925、rs1157651、rs10830963基因型分布

    Table  3.   Distribution of rs1044925, rs1157651, rs10830963 genotypes

    基因型 NAFLD组(n=228) 对照组(n=164) χ2 P
    rs1044925[例(%)] 0.285 0.593
    AA 183(80.26) 128(78.05)
    CC 4(1.75) 2(1.22)
    AC 41(17.98) 34(20.73)
    rs1157651[例(%)] 0.967 0.326
    GG 177(77.63) 134(81.71)
    CC 3(1.32) 0(0)
    GC 48(21.05) 30(18.29)
    rs10830963[例(%)] 0.531 0.767
    GG 47(20.80) 30(18.40)
    CC 75(33.19) 59(36.20)
    GC 104(46.02) 74(45.40)
    注:rs1044925和rs1157651的CC基因型比例低,不适用于χ2检验,因此将其与杂合子合并后进行χ2检验。不同位点因检出率差异,检测数略小于总例数。
    下载: 导出CSV

    表  4  ACAT1 rs1044925不同等位基因携带生化指标比较

    Table  4.   Comparison of biochemical indices of different alleles of ACAT1 rs1044925

    指标 AA基因型携带者 C等位基因携带者 统计值 P
    BMI(kg/m2 26.70±4.85 26.69±3.64 t=0.02 0.99
    TBil(μmol/L) 12.75(10.33~16.68) 13.00(9.98~16.75) Z=-0.07 0.94
    ALT(U/L) 22.97(14.56~35.16) 26.10(17.09~43.52) Z=-1.23 0.22
    AST(U/L) 22.02(18.08~28.67) 22.09(18.64~32.13) Z=-0.71 0.48
    ALP(U/L) 84.91(69.04~100.89) 84.07(69.29~99.70) Z=-0.14 0.89
    GGT(U/L) 25.82(17.07~42.94) 30.00(17.71~48.02) Z=-0.53 0.60
    FPG(mmol/L) 5.04(4.52~5.76) 5.19(4.62~5.87) Z=-1.14 0.25
    TC(mmol/L) 5.09(4.31~5.76) 4.92(4.27~5.56) Z=-1.07 0.29
    TG(mmol/L) 1.42(0.94~2.1) 1.47(1.04~2.2) Z=-0.78 0.44
    LDL(mmol/L) 3.13(2.63~3.57) 2.81(2.32~3.45) Z=-2.08 0.04
    HDL(mmol/L) 1.21(1.05~1.40) 1.16(1.03~1.34) Z=-0.38 0.38
    下载: 导出CSV

    表  5  ACAT1 rs1157651不同等位基因携带生化指标比较

    Table  5.   Comparison of biochemical indices of different alleles of ACAT1 rs1157651

    指标 GG携带者 C等位基因携带者 统计值 P
    BMI(kg/m2 26.47±4.46 27.51±5.14 t=-1.65 0.10
    TBil(μmol/L) 13.05(10.30~16.80) 12.20(10.45~15.90) Z=-0.90 0.37
    ALT(U/L) 23.00(14.65~37.05) 23.17(16.46~35.35) Z=-0.40 0.69
    AST(U/L) 22.06(18.62~29.85) 22.07(18.02~28.25) Z=-0.31 0.76
    ALP(U/L) 84.75(68.98~101.77) 84.70(73.16~100.35) Z=-0.15 0.88
    GGT(U/L) 24.91(16.86~43.23) 28.00(19.05~47.76) Z=-1.44 0.15
    FPG(mmol/L) 5.06(4.55~5.74) 5.12(4.50~6.59) Z=-1.19 0.23
    TC(mmol/L) 5.00(4.34~5.77) 5.10(4.21~5.66) Z=-0.74 0.46
    TG(mmol/L) 1.38(0.94~2.12) 1.67(1.05~2.20) Z=-0.96 0.34
    LDL(mmol/L) 3.10(2.56~3.56) 3.12(2.54~3.51) Z=-0.44 0.66
    HDL(mmol/L) 1.22(1.06~1.40) 1.12(0.99~1.33) Z=-1.94 0.05
    下载: 导出CSV

    表  6  MTNR1B rs10830963不同等位基因携带生化指标比较

    Table  6.   Comparison of biochemical indices of different alleles of MTNR1B rs10830963

    指标 G等位基因携带者 CC携带者 统计值 P
    BMI(kg/m2 26.50±4.05 26.90±5.25 t=-0.75 0.45
    TBil(μmol/L) 13.20(10.60~16.80) 12.15(10.13~16.58) Z=-0.89 0.37
    ALT(U/L) 23.00(15.19~37.43) 23.30(14.47~36.34) Z=-0.17 0.87
    AST(U/L) 22.28(18.13~30.43) 21.77(18.64~28.13) Z=-0.45 0.65
    ALP(U/L) 84.58(70.61~102.29) 84.36(68.34~100.35) Z=-0.23 0.82
    GGT(U/L) 27.00(17.95~44.21) 24.22(16.22~44.17) Z=-0.98 0.33
    FPG(mmol/L) 5.14(4.65~5.88) 4.90(4.39~5.39) Z=-3.01 <0.01
    TC(mmol/L) 4.98(4.28~5.70) 5.09(4.64~5.77) Z=-0.96 0.49
    TG(mmol/L) 1.46(1.04~2.12) 1.42(0.89~2.21) Z=-0.56 0.58
    LDL(mmol/L) 3.08(2.53~3.51) 3.16(2.61~3.60) Z=-0.88 0.38
    HDL(mmol/L) 1.18(1.05~1.38) 1.22(1.03~1.38) Z=-0.08 0.94
    下载: 导出CSV
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