The Correlation Study Of P53 Gene Codon 72 Polymorphism And Dyslipidemia

Objective:A case-control study to analyze the genotype distribution and allele frequencies of p53 gene codon 72 single nucleotide polymorphisms in normal population and dyslipidemia population. This research was to explorer the relationship between p53 gene codon 72polymorphism and dyslipidemia. Methods:(1) In this paper, the research objects were Han population in Luzhou of Sichuan who age over 40, and among individuals without genetic relationship. According to the epidemiological information and clinical laboratory test results, the people were divided into two groups:normal control group of 686 cases, male 194 cases, female 492 cases; dyslipidemia group of 564 cases, male 155 cases, and female 409 cases. (2) Genomic DNA was extracted from blood samples. P53 gene codon 72polymorphism genotypes were detected by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) method. To verify the accuracy of defined genotype by DNA sequencing and to calculate the frequency of genotype and allele. (3)Statistical analysis:all the data were analyzed with the IBM SPSS 19.0 Statistical software package. The distribution balances of genotype were verified by Hardy-Weinberg equilibrium law. The difference of distribution of genotype and allele were detected by chi square test. Value of OR and 95% confidence interval (95%CI) were calculated. Clinical data were analyzed by independent samples t test. Results:(1) The two groups of normal control and dyslipidemia were matched in age, sex distribution. Comparison of clinical data and genotypes in control and dyslipidemia groups, the TC, TG, LDL-C, BMI and WC were increased in dyslipidemia group (P<0.001). FBG,2hPBG, ALT, AST, Cr, SBP and DBP levels in dyslipidemia group were increased than normal control group but without out range of clinical standard (P< 0.001). (2) The distribution of genotype show that the p53 gene codon 72 polymorphism in population were in accord with the genetic equilibrium by Hardy-Weinberg equilibrium law test (P>0.05). (3) Compared with the reference database of NCBI gene polymorphism data, the distribution of p53 gene codon 72 polymorphism in this study is similar to the Asian population, but different from Europe and Africa American population. (4) The difference of genotype frequency in normal control group and dyslipidemia group was statistically significant (P=0.046), but allele frequency differences was not significant (P>0.05). Compared to those with Pro+Arg/Pro genotype, Arg genotype may increased the risk of dyslipidemia by 33.2%(OR=1.332,95%CI:1.049-1.693, P=0.019). (5) Further analyzed the sex differences, the genotype frequencies of women between the two groups were significantly different (P=0.031), allele frequency was not significant (P>0.05). Carrying Arg genotype could increased risk of dyslipidemia in female population was 44.1%(OR=1.441,95%CI: 1.088-1.908, P=0.011). The genotype and allele frequency differences in male were no significant (P>0.05). (6) Analyzed the genotype and allele difference between dyslipidemia subtype in female, compared with the control group, the genotype difference in female hypercholesterolemia were statistically significant (P=0.024, P=0.019). Carrying the Arg genotype increased risk of hypercholesterolemia in female population by 60.9%(OR=1.609,95%CI: 1.143～2.266, P=0.006). Between the mixed hyperlipidemia women and the control group, the difference between the genotype frequency distribution was significantly (P=0.042), allele frequency differences was not significant statistically (P>0.05). The Arg genotype increased the risk of mixed hyperlipidemia among women by 55.5%(OR=1.555,95%CI:1.067～2.267, P=0.021). (7) Comparison of clinical data and genotypes of all study groups, WC, TC, TG and LDL-C levels could increased in Arg genotype people. Furthermore, blood TC, TG, LDL-C levels increased significantly in female population with Arg genotype (P<0.05). Conclusion:(1) The differences of genotype and allele distribution were significantly different between dyslipidemia group and normal control group. There is a correlation between dyslipidemia and p53 gene codon 72 polymorphism. (2)The distributions of genotype and allele gene frequency of p53 gene codon 72 polymorphism were different between different regions and populations. (3)Compared with Pro and Pro/Arg genotype, Arg genotype increased dyslipidemia risk among women but not among in man. (4)Arg genotype may be a risk factor for female hypercholesterolemia and mixed hyperlipidemia. (5) The genotype of Arg in women with high TC, TG, LDL-C level.