| OBJECTIVE: To investigate the association between adenosine-activated protein kinase(AMPK)alpha 1 subunit(PRKAA1)gene polymorphism and the genetic susceptibility of HBV-related hepatitis B(CHB),liver cirrhosis(LC)and hepatocellular carcinoma(HCC)by detecting the polymorphisms at three sites: rs3792822,rs10036575 and rs154268 of PRKAA1,and to evaluate the correlation between PRKAA1 gene polymorphism and HBV-related hepatitis B(CHB),liver cirrhosis(LC)and hepatocellular carcinoma(HCC).It provides valuable genetic markers for the risk of liver disease,and theoretical basis for clinical targeted treatment.Methods: A total of 571 cases were included in this study,including 425 cases in case group,138 cases in chronic hepatitis B group,137 cases in cirrhosis group,150 cases in hepatocellular carcinoma group and 146 cases in healthy control group.The polymorphism of PRKAA1 gene rs3792822,rs10036575 and rs154268 were detected by SNa Pshot sequencing(also known as small sequencing).Then the allele and genotype frequencies of each group of three loci were calculated.The Hardy-Weinberg equilibrium(HWE)law of population genetics was used to analyze whether the selected subjects came from the same Mendelian population and whether they were representative and comparable.The odds ratio(OR)and 95% confidence interval(CI)were calculated by logistic regression analysis after adjusting for age and gender in order to analyze the association of three single nucleotide polymorphisms(SNP)of PRKAA1 gene and HBV-related CHB,LC and HCC genetic.Using the online software SHEsis to constructe the haplotypes of PRKAA1 rs3792822,rs10036575 and rs154268,and analyze their association of genetic susceptibility to CHB,HBV-LC and HBV-HCC.Results 1.A total of 570 subjects were included in our study.There were 146 patients in the control group,including 120 males(82.2%),26 females(17.8%),with an average age of(48.24±11.41).138 males in the CHB group,including 108 males(78.3 %),30 women(21.7%),with an average age of(39.71±11.69);137 patients in LC group,including 108 males(78.7%),29 females(21.3%),with an average age of(47.04±11.69);150 patients in HCC group,including 127 males(84.7%)and 23 females(15.7%),with an average age of(50.53±10.35).There was no significant difference in gender ratio between the case groups and the control group(P>0.05).The variance analysis showed that the average age difference of the four study groups was statistically significant(P<0.05).The average age of CHB group was significantly lower than that of the other three groups(P<0.05).The average age difference between LC group and HCC group was statistically significant(P<0.05).The average between LC group and control group,HCC group and control group were no significant difference(P>0.05).The genotype distribution frequencies of PRKAA1 gene rs3792822,rs10036575 and rs154268 in each case group and control group were consistent with the Ha-war equilibrium law(both P>0.05).2.The rs3792822 locus of PRKAA1 gene has three genotypes of GG,GA and AA.Compared with the control group,the frequencies of the three genotypes and alleles of the PRKAA1 gene rs3792822 locus were not significantly difference between the CHB group,the LC group and the HCC group(both P>0.05).3.PRKAA1 gene rs1003657 has three genotypes of TT,TC and CC.Compared with the control group,the frequency of TT genotypes in the HCC group was lower(P<0.05),but there was no statistical difference between the cases(P>0.05).In the male and female populations,there was no significant difference in the frequency of carrying all three genotypes and alleles(both P>0.05).Compared with the control group,the TC genotype in the ?50-year-old population increased the risk of LC and HCC.The OR value and 95% CI were: OR=3.851,95% CI: 1.316-11.272,P=0.014;OR = 2.633,95% CI: 1.074-4.658,P = 0.034.4.The rs154268 locus of PRKAA1 gene has three genotypes of CC,CT and TT.Compared with the control group,the frequencies of the three genotypes and alleles of the PRKAA1 gene rs154268 locus were not significantlyConclusion 1.PRKAA1 gene rs1003657 site mutation genotype CC can increase the risk of HCC in healthy people,and heterozygous TC genotype can increase the risk of LC and HCC in people over 50 years old.2.PRKAA1 gene rs154268 carries the allele T to increase the risk of LC in healthy women.3.The PRKAA1 gene rs3792822 polymorphism was no significant associated with the risk of HBV-related chronic hepatitis,cirrhosis and hepatocellular carcinoma.4.The haplotypes of PRKAA1 gene rs3792822,rs10036575 and rs154268 were not significant associated with the risk of HBV-related chronic hepatitis,cirrhosis and hepatocellular carcinoma. |
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