Association study on polymorphisms of cAMP signaling pathway with recurrent major depressive disorder / 中华行为医学与脑科学杂志

Objective@#To investigate the possible role of tag single nucleotide polymorphisms in cAMP signaling pathway in patients with recurrent major depressive disorder in Chinese Han population.@*Methods@#1 030 patients with recurrent major depressive disorder according to the DSM-Ⅳ criteria were recruited as case group and 851 age- and gender- matched healthy volunteers were recruited as control group.The sequenom mass spectrometry method was adopted to explore the genotype and allele frequency distributions of tag single nucleotide polymorphisms of cAMP signaling pathway in the two groups.@*Results@#The differences of genotype and allele frequencies of the ADCY7 gene loci rs1064448 and HTR2A gene loci rs17068986 were significant between case group and control group(P<0.05). The difference of the genotype frequencies(492∶423∶112, 356∶401∶91; 538∶392∶94, 414∶371∶61; 24∶165∶838, 3∶150∶694; 219∶468∶337, 139∶418∶237; 153∶481∶393, 115∶446∶286; 53∶286∶688, 25∶296∶524)of the ADCY9 gene loci rs2531995, BDNF gene loci rs10835210, rs7124442, CREB1 gene loci 4675690, rs2551645 and the HTR2A gene loci rs3125 were significant in case-control group(P<0.05); while the rest tagSNPs had no statistical difference in genotype and allele distribution frequencies in case-control group(P>0.05). In gender-specific analyses, the differences of the genotype and allele frequencies of the ADCY7 gene loci rs106448 and CREB1 gene loci rs2551645 were significant in male case-control group(P<0.05); the differences of the genotype(195∶177∶49, 193∶423∶41; 221∶158∶42, 237∶201∶28; 83∶188∶148, 85∶237∶122; 24∶113∶284, 10∶176∶281)of the ADCY9 gene loci rs2531995, BDNF gene loci rs10835210, CREB1 gene loci rs4675690, and HTR2A gene loci rs3125 were significant in male case-control group(P<0.05); while the rest tagSNPs had no statistical difference in genotype and allele distribution frequencies in male case-control group(P>0.05). The differences of the genotype and allele frequencies of the ADCY7 gene loci rs1064448 and HTR2A gene loci rs17068986 were significant in female case-control group(P<0.05). The differences of the genotype(16∶94∶497, 1∶73∶308; 136∶280∶189, 54∶181∶115)of the BDNF gene loci rs7124442 and CREB1 gene loci rs4675690 were significant in female case-control group(P<0.05). The differences of the allele frequencies(840: 372, 493: 267) of the ADCY9 gene loci rs2531995 were significant in female case-control group(P<0.05), while the rest tagSNPs had no statistical difference in genotype and allele distribution frequencies in female case-control group(P>0.05).@*Conclusion@#The ADCY7 gene loci rs1064448 and CREB1 gene loci rs4675690 are associated with recurrent major depressive disorder in Chinese Han population.

Association study on interaction effects of CREB1 gene and BDNF gene polymorphisms and recurrent major depressive disorder / 中华行为医学与脑科学杂志

Objective To investigate the interactions between cAMP-response element-binding protein 1 (CREB 1) gene polymorphisms (rs889895,rs3770704,rs2551645,rs4675690) and brain derived neurotrophic factor (BDNF) gene polymorphisms (rs7124442,rs 10835210) and the association with recurrent major depressive disorder.Methods The blood samples were taken from 768 recurrent major depressive disorder patients and 511 healthy controls.The DNA was isolated from blood samples and was detected by SNP Sequenom Mass Array analysis.Chi-square test was used to compare differences in the frequency distribution of alleles and genotype between depression and controls.The generalized multifactor dimensionality reduction (GMDR) method was used to analyze the gene-gene interaction.Binary logistic regression was used to verify the optimal model.Results After adjusting the factors of sex and age,the GMDR analysis showed rs10835210 was the optimal model.In this model,the testing balanced accuracy was 0.5319 and cross-validation consistency value was 10/10.And rs10835210 had a statistically significant effect on the risk of recurrent major depressive disorder(P=0.0107).There was no significant gene-gene interaction of five tag SNPs on recurrent major depressive disorder(P＞0.05).Binary logistic regression analysis showed the AC contributed to a significantly lower risk of recurrent major depressive disorder than did the CC (OR =0.772,95％ CI=0.608-0.980,P=0.033).It was failed to find the genetic polymorphism of CREB1 rs889895.Conclusion BDNF rs10835210 may be one of the biological markers of recurrent major depressive disorder.

Selecting the tag SNPs of TLR2 gene with bioinformatics techniques / 基础医学与临床

Objective To select the tag SNPs of TLR2 gene in the Chinese population with bioinformatics techniques.Methods We ascertained the assayed scope of the TLR2 gene with the aid of NCBI database and downloaded SNP genotype data of TLR2 gene in the Chinese population from Hapmap database.Then Haploview (version 4.0) was used to calculate linkage disequilibrium (LD) statistics.Haplotype blocks were constructed throughout the TLR2 gene according to the upper and lower 95% confidence bound of the D'value.Meanwhile,we selected the tag SNPs based on r~2 values and the LOD value between SNPs and picked up the representative haplotypes in accordance with the proportion of each haplotype in the haplotype blocks,respectively.Results We constructed 2 haplotype blocks within the TLR2 gene and selected 3 tag SNPs containing 3013 A/G,19216 T/C and 22215 G/T in the Chinese population.Meanwhile,we identified the representative haplotypes of which the tag SNP would be on behalf of every haplotype block.Conclusion The SNPs of 3013 A/G,19216 T/C and 22215 G/T,the most representative SNPs in the whole TLR2 gene in the Chinese population,could be selected as tag SNPs to guide their association studies between the TLR2 gene and sepsis.

Effect of the genetic variants of heme oxygenase-1 gene on blood pressure level in hypertensive pailents / 中国综合临床

Objective To assess the relationship between the polymorphisms of heme oxygenase-1 gene and blood pressure level.Methods With the whole-gene based tagging SNP approach,3 tag SNPs of heme oxygenase-1 gene were selected for study.These tag SNPs were genotyped in 503 essential hypertension cases Blood pressure lev-els among different genotypes of each SNP were compared with ANOVA.The haplo.stats program wa8 employed to test haplotype frequency with blood pressure level.Results Subjects with rs2071749 A allele had the lower blood pressure levels than subjects with GG genotypes(SBP:159.5 mm Hg vs.168.5 mm Hg and DBP:97.6 mm Hg vs.101.3 mm Hg respectively.P<0.05).In the haplotype analyses.Haplotype T-T-A which carried the rs2071749 A allele was found significantly associated with SBP and DBP after adjustment for age,gender,body mass index.8n10k.illg and drinking·Conclusion The genetic variants of heine oxygenase.1 gene misht be associated with blood pres-sure levels.