| Objective:(1)Type 2 diabetes is a common chronic disease,in addition to causing physical discomfort in patients,it is often accompanied by anxiety,depression and other emotional disorders or mental illness.The interaction between depression and diabates can promote the progression of each other,resulting in a "vicious circle",which seriously affects the quality of life of patients and the prognosis of the disease.In order to reveal the molecular mechanism of type 2 diabetes co-morbid with depression from genetic perspective,in this study we conducted an association analysis of the depression susceptibility genes HTR2 A and TPH2 with the risk of type 2 diabetes complicated with depression.(2)To study the incidence of depression in type 2 diabetes mellitus,explore the clinical characteristics of type 2 diabetes mellitus when comlicated with depression,the influence of depression on type 2 diabetes mellitus,and to understand the incidence of type 2 diabetes mellitus patients,risk factors for depression in type 2 diabates mellitus.(3)The HTR2 A and TPH2 gene tag SNPs were selected to analyze their distribution differences between T2 DM and T2 DM combined with depression groups,and the correlation between these SNPs and T2 DM combined with depression was analyzed;further association analysis was carried out to understand whether there was linkage disequilibrium between SNPs of the same gene,the association between the haplotypes formed by linkage and depression in type 2 diabetes mellitus.Reveal the molecular mechanism of the high incidence of depression in type 2diabetes;to clarify the correlation between the SNPs of HTR2 A and TPH2 genes and type2 diabetes complicated with depression,and to discover the possible risk SNP for depression in type 2 diabetes;provide a objective and effective detection method for screening of highrisk groups for depression Methods:(1)A total 874 participants with type 2 diabetes were recruited to this study and the epidemiology data,clinical data questionnaire survey were conducted.The screening of depression was carried by senior psychiatrists used Zung’s Selfrating Depression Scale(SDS)by one-on-one interviews with the research participants.(2)Using chi-square test and t test to analyze whether there were statistical differences in general information between T2 DM and T2 DM combined with depression groups;analyze whether there were differences in clinical indicators between the two groups;logistic regression analysis was used to analyze the influencing factors of type 2 diabetes complicated with depression,and the risk factors of type 2 diabetes complicated with depression.(3)27 tag SNPs of HTR2 A gene and 28 tag SNP of TPH2 gene were selected.The sample DNA was extracted by centrifugal column method,and the SNP loci of HTR2 A gene was genotyped by SNP scan high-throughput sequencing analysis,TPH2 gene were genotyped by im LDR high-throughput sequencing analysis.The Chi-square test was used to analyze the differences in genotype and alleles distribution of each SNP locus between the two groups under co-dominant,dominant and recessive inheritance patterns;chi-square test and logistic regression analysis were used to study the p-value OR value and confidence interval of each SNP locus and depression under co-dominant,dominant,recessive inheritance patterns,and to clarify the assocation of HTR2 A and TPH2 with type 2 diabetes co-morbid with depression.Subsequently,linkage analysis and haplotype association analysis were performed,and logistic regression analysis was used to evaluate the association between the haplotypes formed by linked SNPs and T2 DM complicated with depression.Results:1.A total of 874 type 2 diabetes patients were recruited in this study,234 patients having depression the prevalence of depression in this study is 26.8%.The chisquare test showed that there is there were differences in gender,age,education level,marital status,diabetes duration,Hb A1 c,hypertension,diabetic nephropathy,and the number of complications(p <0.05).Binary Logistic multivariate regression analysis showed that the gender,age,duration of diabetes,illiteracy,Hb A1 c,and diabetic nephropathy were risk factors for depression in patients with type 2 diabetes(p < 0.05).2.Association analysis of HTR2 A gene polymorphism and type 2 diabetes complicated with depression(1)All 27HTR2 A SNPs in these two groups were in line with Hardy-Weinberg equilibrium(p>0.05).(2)Allele frequencies and genotype frequencies between two groups: By analyzing the allele and genotype distribution frequencies of the 27 HTR2 A tag SNPs between two groups it was found that there were 6 SNPs genotype distribution has difference in the co-dominant,dominant and recessive models,which are rs1328676 、 rs17289304 、 rs1328684 、rs4942578、rs77389282、rs1923882.The distribution of allele frequency of rs77389282 was statistically different between the two groups.(3)Association analysis:(4)Haplotype association analysis of HTR2 A gene SNP: no haplotypes related to the onset of depression were found.3.Association analysis of TPH2 SNP gene polymorphisms with type 2 diabetes mellitus complicated with depression:(1)Hardy-Weinberg Equation test: two loci rs1352251 and rs6582072 does not meet the Hardy-Weinberg Equation test.The remaining sites are in line with Hardy-Weinberg equilibrium.(2)After analyzing the allele and genotype distribution frequencies of 28 tag SNPs in the TPH2 gene between the two groups,there were 4 SNPs genotype distribution has significant differences,And there are 2 SNPs has significant differences in the allele distributions.The genotype frequencies of the rs12228278 locus were statistically different between the two groups under the dominant and co-dominant models.Under the dominant model,the genotype distribution frequencies of rs12231341 and rs1473473 loci were statistically different between the two groups.The allele frequencies of rs12228278 and rs12231341 were significantly different between the two groups.The A allele of rs12228278 was a risk factor for depression in patients with type 2 diabetes,and the T allele of rs12231341 was a protective factor.(3)Association analysis: The rs12228278,rs12231341,and rs1473473 loci were protective factors for type2 diabetes,respectively,and rs10879353 was a risk factor for type 2 diabetes complicated with depression.(4)Haplotype association analysis: The rs11179024-rs7305115-rs1023989-rs55851729-rs10506646-rs4760820 constitutes the GAAGGC haplotype,the AGGCT haplotype composed of rs1023989-rs55851729-rs10506646-rs4760820-rs1473473,these two haplotypes was significantly associated with type 2 diabetes complicated with depression.Conclusion:(1)Type 2 diabetes patient were susceptible to depression;depression is common in patients with type 2 diabetes;the prevalence of depression is higher in patients with type 2 diabetes when compared with those without type 2 diabetes;comorbid with depression cause poor glycemia control,poor quality of life.(2)The 27 tag SNPs of HTR2 A gene have differences in the distribution between type 2diabetes patient group and type 2 diabetes with depression patient group,and some SNP are related to the depression.Rs77389282 C/A genotype and G/T genotype of rs4942578 are risk factors for depression in patients with type 2 diabetes.(3)Some of the 28 tag SNPs of TPH2 gene have different distributions between type 2 diabetes patient group and the type2 diabetes with depression patient group,and some SNPs are related to the depression,controls the susceptibility of patients with type 2 diabetes to depression;rs1228278,rs1473473,rs12231341 are protective factors for depression,and the recessive model of rs10879353 C/C genotype can increase the risk of depression.(4)HTR2A gene rs77389282,rs4942578,TPH2 gene rs10879353 loci can be used to screen high-risk depression groups in clinical practice. |
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