ABCB11基因变异与原发性肝内胆管结石的相关性研究

Correlation of variations of ABCB11 gene and primary intrahepatic stone

    摘要
  • 摘要: 目的:探讨ABCB11基因变异与原发性肝内胆管结石(PIS)发病的关系。
    方法:采用回顾性病例对照研究方法。收集2012年12月至2015年12月第三军医大学西南医院收治的319例PIS患者和同期344例健康体检者的临床资料。319例PIS患者设为PIS组，344例健康体检者设为对照组。采用PCR和DNA测序方法，检测ABCB11基因27个外显子。观察指标：(1)PIS组患者和对照组受试者 ABCB11基因变异及基因型频率分布。(2)ABCB11基因变异与PIS患者临床资料的相关性分析：临床资料包括术前肝功能检验指标、胆管炎反复发作、术前梗阻性黄疸、结石性质、结石复发。ABCB11基因变异及基因型频率分布的组间比较采用Logistic回归分析。ABCB11基因的基因型与PIS患者术前肝功能检验结果的相关性采用KruskalWallis H检验分析。ABCB11基因的基因型与PIS患者临床病理资料的相关性采用x2检验分析。
    结果:(1)PIS组患者和对照组受试者ABCB11基因变异及基因型频率分布： PIS组319例患者ABCB11基因全外显子测序结果显示有6个变异位点，分别为rs3815675(同义突变)、rs2287616(同义突变)、rs2287617(错义突变)、rs2287622(错义突变)、rs118109635(错义突变)、rs497692(同义突变)位点，分别位于第4、9、9、13、21、24号外显子上。PIS组rs118109635位点的CT基因型频率分别为4.70%(15/319)，对照组为1.45%(5/344)，两组比较，差异有统计学意义(OR=3.49，95%可信区间：1.17～10.40， P<0.05)。PIS组rs497692位点的GG、AG+GG基因型频率分别为46.08%(147/319)、87.46%(279/319)，对照组分别为37.79%(130/344)、79.36%(273/344)，两组比较，差异均有统计学意义(OR=1.73，1.65，95%可信区间：1.05～2.83，1.04～2.61，P<0.05)。(2)ABCB11基因变异与PIS患者临床资料的相关性分析： rs118109635位点的CC基因型PIS患者GGT、ALP、DBil水平分别为167 U/L(7～1 968 U/L)、166 U/L (36～1 527 U/L)、4 μmol/L(1～272 μmol/L)，CT基因型PIS患者分别为433 U/L(17～864 U/L)、232 U/L(85～613 U/L)、6 μmol/L(2～173 μmol/L)，两者比较，差异均有统计学意义(H=6.025，5.879，8.056，P<0.05)。rs497692位点的AA、AG、GG型PIS患者球蛋白水平分别为32 g/L(20～40 g/L)、34 g/L(17～50 g/L)、 33 g/L(14～49 g/L)，3者比较，差异有统计学意义(H=12.119，P<0.05)。81例PIS复发患者中，ABCB11基因rs2287617位点的GG、GA型分别为78、3例，两者比较，差异有统计学意义(x2=5.367，P<0.05)；rs2287622位点的TT、TC、CC型分别为12、39、30例，3者比较，差异有统计学意义(x2=6.153，P<0.05)。127例术前有梗阻性黄疸的PIS患者中，ABCB11基因rs118109635位点的CC、CT型分别为116、11例，两者比较，差异有统计学意义(x2=7.381，P<0.05)；rs497692位点的AA、AG、GG型分别为11、43、73例，3者比较，差异有统计学意义(x2=11.364，P<0.05)。
    结论:ABCB11基因变异位点rs118109635 和 rs497692与PIS患者发病相关，并且上述变异位点与PIS患者的胆道梗阻、胆汁淤积等变化有关。

     

    Abstract: Objective:To investigate the correlation of variations of ABCB11 gene and primary intrahepatic stone (PIS).
    Methods:The retrospective casecontrol study was conducted. The clinical data of 319 patients with PIS and 344 healthy controls who were admitted to the Southwest Hospital of the Third Military Medical University between December 2012 and December 2015 were collected. Three hundred and ninteen patients with PIS and 344 healthy controls were respectively allocated into the PIS and control groups. Twentyseven exons in ABCB11 gene were detected via polymerase chain reaction (PCR) and DNA sanger sequencing. Observation indicators included: (1) variations and genotype frequency distribution of ABCB11 gene in the 2 groups; (2) correlation analysis between variations of ABCB11 gene and clinical data of patients with PIS: preoperative indicators of liver function test, recurrent episodes of cholangitis, preoperative obstructive jaundice, type and recurrence of stones. Comparison between groups in variations and genotype frequency distribution of ABCB11 gene was analyzed by the Logistic regression. The KruskalWallis H test was performed to explore the correlation between genotype of ABCB11 gene and clinical test results of patients with PIS. Correlation between genotype of ABCB11 gene and clinicopathological data of patients with PIS was analyzed by the chisquare test.
    Results:(1) Variations and genotype frequency distribution of ABCB11 gene in the 2 groups: wholeexome sequencing results showed that synonymous mutations of rs3815675, rs2287616 and rs497692 and missense mutations of rs2287617, rs2287622 and rs118109635 in the PIS group were respectively detected in exon 4, 9, 24 and 9, 13 , 21. CT genotype frequency of rs118109635 was 4.70%(15/319) in the PIS group and 1.45% (5/344) in the control group, respectively, with a statistically significant difference ［OR=3.49, 95% confidence interval (CI): 1.17-10.40, P<0.05］. GG and AG＋GG genotype frequency of rs497692 were 46.08%(147/319), 87.46%(279/319) in the PIS group and 37.79%(130/344), 79.36%(273/344) in the control group, respectively, with a statistically significant difference (OR=1.73, 1.65, 95% CI: 1.05-2.83, 1.04-2.61, P<0.05). (2) Correlation analysis between variations of ABCB11 gene and clinical data of patients with PIS: levels of glutamyltranspeptidase (GGT), alkaline phosphatase (ALP) and direct bilirubin (DBil) in the PIS group were 167 U/L (range, 7-1 968 U/L), 166 U/L (range, 36-1 527 U/L), 4 μmol/L(range, 1-272 μmol/L) in the CC genotype of rs118109635 and 433 U/L(range, 17-864 U/L), 232 U/L (range, 85-613 U/L), 6 μmol/L(range, 2-173 μmol/L) in the CT genotype of rs118109635, respectively, with a statistically significant difference (H=6.025, 5.879, 8.056, P<0.05). Globulin level of PIS group was respectively 32 g/L(range, 20-40 g/L), 34 g/L(range,17-50 g/L) and 33 g/L(range,14-49 g/L) in the AA, AG and GG genotype of rs497692, respectively, with a statistically significant difference (H=12.119, P<0.05). Of 81 patients with recurrence of PIS, GG and GA genotypes of rs2287617 were detected in 78 and 3 patients, respectively, with a statistically significant difference (x2=5.367, P<0.05); TT, TC and CC genotypes of rs2287622 were detected in 12, 39 and 30 patients, respectively, with a statistically significant difference (x2=6.153, P<0.05). Of 127 patients with obstructive jaundice, 116 and 11 patients had CC and CT genotypes of rs118109635, respectively, with a statistically significant difference (x2=7.381, P<0.05); 11, 43 and 73 patients had AA, AG and GG genotypes of rs497692, respectively, with a statistically significant difference (x2=11.364, P<0.05).
    Conclusion:There is a correlation between rs118109635 and rs497692 of ABCB11 gene and PIS, meanwhile, the above variation loci are associated with obstruction of biliary tract and cholestasis.

     

    • HTML全文
    • 参考文献(0)
    • 相关文章
    • 施引文献
  • 资源附件(0)

/

返回文章
返回