Association Of DNA Polymorphisms Within CYP11B2 And CYP11B1 Locus With The Risk And Prognosis Of Aldosterone Producing Adenoma

Objective:To investigate the association of DNA polymorphisms within CYP11B2 and CYP11B1 locus with the risk and prognosis of Aldosterone Producing Adenoma(APA).Methods:The blood samples from 68 patients with APA(APA group) were collected from the First Affiliated Hospital of Gannan Medical University and Chinese PLA General Hospital, 80 normal people or hospitalized patients without adrenal related diseases, no family history of hypertension, cardiovascular disease, cancer and other diseases(Control group) were collected from the First Affiliated Hospital of Gannan Medical University. Two groups were Han Chinese population. CYP11B2 and CYP11B1 gene polymorphisms were detected by Real-time PCR Taq Man-MGB 5’-nuclease assay.The correlation between the CYP11B2 and CYP11B1 polymorphisms and APA was analyzed by the online SHEsis software. The postoperative blood pressure recovery of APA patients was followed up, and the Logistic regression model was adopted to analyze the prognosis influence factors of APA.Results:Age and gender in APA patients compared with controls had no statistically significant differences(P>0.05), but systolic blood pressure and diastolic blood pressure were significantly higher in APA patients than that in controls, and serum potassium ion concentration was lower in the APA patients compared with controls(P<0.05). The distribution frequencies of four SNPs genotype in the two groups followed the Hardy-Weinberg Equilibrium(P>0.05). The frequency of the A and G alleles of rs3802228 in APA and control group were 75.7%, 24.3% and 64.4%, 35.6%,respectively(P<0.05). The distribution of the A and G alleles of rs6433 in APA andcontrol group were 75.7%, 24.3% and 86.9%, 13.1%, respectively(P<0.05).The frequency of the G and A alleles of rs5301 in APA and control group were 75.7%,24.3% and 86.9%, 13.1%, respectively(P<0.05). There was no statistically significant difference between the two groups with the genotypes frequency for rs3802228, rs6433 and rs6532040(P>0.05). The distribution frequencies of the C and A alleles of rs6471570 in APA and control group were 72.8%, 27.2% and 74.4%,25.6%, respectively(P>0.05). The frequency of the CC, AC and AA genotype were55.9%, 33.8% and 10.3% in APA group, and 51.2%, 46.3% and 2.5% in control group.The risk for APA of AC genotype was 0.178 times that of AA genotype(P<0.05,OR=0.178, 95% CI=0.034~0.930); with CC genotype was no statistical significance(P>0.05, OR=0.265, 95% CI=0.052~1.355). CYP11B2 and CYP11B1 gene haplotype analysis showed that haplotype A-G-A-A was positively correlated with the formation of the APA(OR=2.431, 95% CI=1.288~4.578), but haplotype G-A-G-A was negatively correlated with the formation of the APA(OR=0.061, 95%CI=0.008~0.458). Postoperative blood pressure recovery had no relationship with rs3802228, rs6433, rs5301 and rs6471570 genotype(P>0.05). CYP11B2 and CYP11B1 gene haplotype analysis showed that haplotype had no relationship with postoperative blood pressure recovery(P>0.05). Logistic regression analysis showed that posteroperative blood pressure recovered more better in those with lower BMI,less of types of preoperative control of blood pressure medication, and higher preoperative sensitive to spironolactone rate in APA group(P<0.05).Conclusions:1. CYP11B2 and CYP11B1 gene polymorphisms were associated with the formation of APA. APA negatively correlated with genotype AC of rs6471570 and haplotype G-A-G-A, but positively correlated with Haplotype A-G-A-A.2. The genotype of rs3802228, rs6433, rs5301, rs6471570 and the haplotype made up of them that locate on CYP11B2 and CYP11B1 gene had no relationship with postoperative blood pressure recovery.3. BMI, types of preoperative control of blood pressure medication, and sensitivity to spironolactone before preoperative were influence factors ofpostoperative blood pressure recovery of APA patients.