Association Between Single Nucleotide Polymorphisms Of Adenylate Cyclase And Recurrent Major Depressive Disorder

Objective To investigate the possible role of single nucleotide polymorphisms of the adenylate cyclase gene among patients with recurrent major depressive disorder in Chinese Han population.Methods 1. In the case-control study, 397 patients(173 males, 216 females) with recurrent major depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders IV criteria were recruited in the study, the normal control group included 441(209 males, 232 females) age and gender matched healthy volunteers recruited from the same region of the Chinese han population. According to the National Center for Biotechnology Information Database and the related documents, ADCY3 rs11676272, ADCY7 rs1064448 and ADCY9 rs2531982, rs2531995, rs7196832, rs8061182 were detected,and the genotyping of the six tag SNPs was performed using Sequenom mass spectrometry method to investigate genotype and allele frequency distribution in case and control groups.2. Statistical analyses were performed using the SPSS 21.0 software package. The independent samples t test was used to determine the difference in mean age between the case group and the control group. The Hardy-Weinberg equilibrium was tested with Pearson's chi-square test. and the chi-square test was used to compare the distribution of genotype and allele between the case group and the control group. The Pearson's chi-square test was used to compare the distribution of genotype and allele between the patient and control group. P <0.05 was considered statistically significant.Results 1. The Hardy-Weinberg equilibrium of six SNPs in case and control group There was no difference in the ratio of sex between the case group and the control group(all P > 0.05). Similarly, no statistically significant difference was evident for the mean age in case and control subjects(all P > 0.05). Genotype distributions of five tag SNPs(ADCY3rs11676272, ADCY7 rs1064448 and ADCY9 rs2531982, rs2531995, rs7196832) were in the Hardy-Weinberg equilibrium, both in the case group and the control group(all P > 0.05). In case group, the genotype distribution of ADCY9 rs8061182 wasn't in the Hardy-Weinberg equilibrium,(?2= 4.42041, P= 0.03551), while in the control group, the genotype distribution of ADCY9 rs8061182 was in the Hardy-Weinberg equilibrium( P > 0.05). 2. Comparison of six SNPs in case and control group There was no statistically difference evident in genotype and allele distribution frequencies of ADCY3 rs11676272, ADCY7 rs1064448 and ADCY9 rs2531982, rs2531995, rs7196832, rs8061182 between the case group and the control group(all P > 0.05).3. Comparison of high recurrence and low recurrence in patients with six SNPs The GA genotype distribution in high recurrence patients for ADCY3 rs11676272 was higher than that of low recurrence patients, and the difference was significant(?2=7.085, P=0.008), G allele frequency in high recurrence patients for ADCY3rs11676272 was higher than that of low recurrence patients(?2=3.828, P=0.050). No significant difference was detected in genotype or allele distribution frequencies between high recurrence and low recurrence group in case patients for ADCY7 rs1064448 and ADCY9 rs2531982, rs2531995, rs7196832, rs8061182(all P > 0.05). 4. The relationship between duration and 6 SNPs The GA genotype of ADCY3 rs11676272 in short duration patients has a high frequency than the long duration patients in case group, and the difference was significant(?2=6.883, P=0.009), while no significant difference was detected in allele frequency between the long duration patients and short duration patients for ADCY3 rs11676272(?2=0.553, P=0.457). There was no statistically difference evident in genotype or allele frequencies between the long duration and short duration group in case patients for ADCY7 rs1064448 and ADCY9 rs2531982, rs2531995, rs7196832, rs8061182(all P > 0.05).Conclusions 1. Rs11676272 of ADCY3 is associated with a high recurrence tendency and short duration of onset of depression in Chinese Han population, it may be the susceptibility gene for recurrent major depressive disorder patients. 2. ADCY9 rs8061182 may be a slight mutation, and it is worthy of further attention. 3. No difference in genotype and allele distribution of rs1064448 of ADCY7,rs2531982,rs2531995,rs7196832 of ADCY9 was found in the recurrent major depressive disorder in Chinese han population.