Dataset Information

Genetic distribution and association analysis of DRD2 gene polymorphisms with major depressive disorder in the Chinese Han population.

ABSTRACT: Dopamine D2 receptor is involved in reward-mediating mesocorticolimbic pathways. It plays an important role in major depressive disorder (MDD). Three gene polymorphisms Taq1A, C957T and -141C ins/del, were identified in the DRD2 gene among the Western population. These variants in the DRD2 gene might be associated with the susceptibility of MDD patients through affecting the bioeffects of endogenous dopamine neurotransmission. However, little is known about their occurrence in Chinese population and their association with the susceptibility of patients with major depressive disorder. In this study, a total of 338 unrelated adult Chinese Han population, including 224 healthy volunteers and 114 patients with major depressive disorder, were recruited. DRD2 polymorphisms (Taq1A and -141C ins/del) were detected using restriction fragment length polymorphism (RFLP) analysis and the C957T were detected by sequencing directly. As a result, three polymorphisms were identified in Chinese Han population and all were common SNP. However, we could detect no evidence of genetic association between 3 markers in DRD2 and major depressive disorder in the Chinese Han population. To conclude, this result suggests that Taq1A, C957T and -141C ins/del of DRD2 gene may not be associated with major depressive disorder, also may be the sample sizes too small to allow a meaningful test.

SUBMITTER: He M

PROVIDER: S-EPMC3657369 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Genetic distribution and association analysis of DRD2 gene polymorphisms with major depressive disorder in the Chinese Han population.

He Mei M Yan Hong H Duan Zhao-Xia ZX Qu Wei W Gong Hai-Yan HY Fan Zheng-Li ZL Kang Jian-Yi JY Li Bing-Cang BC Wang Jian-Min JM

International journal of clinical and experimental pathology 20130515 6

Dopamine D2 receptor is involved in reward-mediating mesocorticolimbic pathways. It plays an important role in major depressive disorder (MDD). Three gene polymorphisms Taq1A, C957T and -141C ins/del, were identified in the DRD2 gene among the Western population. These variants in the DRD2 gene might be associated with the susceptibility of MDD patients through affecting the bioeffects of endogenous dopamine neurotransmission. However, little is known about their occurrence in Chinese population ...[more]

PMID: 23696934

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Project description:BACKGROUND:The D2 dopamine receptor (DRD2) has been extensively investigated and has been associated with the occurrence of neuropsychiatric disorders. Polymorphisms in the DRD2 gene have also been determined as a possible predisposing component for major depressive disorders (MDD). The present study focused on evaluating the connection of polymorphisms inside the whole DRD2 gene in MDD patients as well as in non-MDD participants in a group selected from the Chinese Han population. MATERIALS AND METHODS:In total, 831 unrelated Chinese adults from the Han population were sampled, including 497 non-MDD participants and 334 MDD patients for this evaluation. After the haplotype bins were built, 14 tag single-nucleotide polymorphisms (tSNPs) and the two most investigated SNP were chosen for the whole DRD2 gene. An improved multiplex ligation detection reaction (iMLDR) technique was used to choose the genotypes. Following this, the allelic frequencies and clinical features were contrasted between the two independent Chinese Han populations. Transcriptional enhancer activities were measured to assess the functionality of the rs7131056 polymorphism. RESULTS:Sixteen SNPs were identified, including the two most examined in the Chinese Han population, and all were recurrent SNPs. Of the 16 SNPs, two (rs4648317 and rs7131056) were significantly connected to MDD. Patients with MDD were more apt to carry the rs4648317G and rs7131056A allele in contrast to the non-MDD controls (P < 0.05). The genetic risk effect on MDD occurrence was associated with the haplotype GTGATCGCGCAGGC of fourteen tag SNPs (OR = 1.52, 95% CI: 1.06 to 2.18, P = 0.02). Moreover, the rs7131056 polymorphism contained intronic silencer activities. CONCLUSIONS:This case-control evaluation involving the Chinese Han population suggests that the rs4648317 and rs7131056 polymorphisms and the haplotype GTGATCGCGCAGGC inside the DRD2 gene could be possible markers to forecast vulnerability to MDD.

Project description:ImportanceDespite the moderate, well-demonstrated heritability of major depressive disorder (MDD), there has been limited success in identifying replicable genetic risk loci, suggesting a complex genetic architecture. Research is needed to quantify the relative contribution of classes of genetic variation across the genome to inform future genetic studies of MDD.ObjectivesTo apply aggregate genetic risk methods to clarify the genetic architecture of MDD by estimating and partitioning heritability by chromosome, minor allele frequency, and functional annotations and to test for enrichment of rare deleterious variants.Design, setting, and participantsThe CONVERGE (China, Oxford, and Virginia Commonwealth University Experimental Research on Genetic Epidemiology) study collected data on 5278 patients with recurrent MDD from 58 provincial mental health centers and psychiatric departments of general medical hospitals in 45 cities and 23 provinces of China. Screened controls (n = 5196) were recruited from a range of locations, including general hospitals and local community centers. Data were collected from August 1, 2008, to October 31, 2012.Main outcomes and measuresGenetic risk for liability to recurrent MDD was partitioned using sparse whole-genome sequencing.ResultsIn aggregate, common single-nucleotide polymorphisms (SNPs) explained between 20% and 29% of the variance in MDD risk, and the heritability in MDD explained by each chromosome was proportional to its length (r = 0.680; P = .0003), supporting a common polygenic etiology. Partitioning heritability by minor allele frequency indicated that the variance explained was distributed across the allelic frequency spectrum, although relatively common SNPs accounted for a disproportionate fraction of risk. Partitioning by genic annotation indicated a greater contribution of SNPs in protein-coding regions and within 3'-UTR regions of genes. Enrichment of SNPs associated with DNase I-hypersensitive sites was also found in many tissue types, including brain tissue. Examining burden scores from singleton exonic SNPs predicted to be deleterious indicated that cases had significantly more mutations than controls (odds ratio, 1.009; 95% CI, 1.003-1.014; P = .003), including those occurring in genes expressed in the brain (odds ratio, 1.011; 95% CI, 1.003-1.018; P = .004) and within nuclear-encoded genes with mitochondrial gene products (odds ratio, 1.075; 95% CI, 1.018-1.135; P = .009).Conclusions and relevanceResults support a complex etiology for MDD and highlight the value of analyzing components of heritability to clarify genetic architecture.

Dataset Information

Genetic distribution and association analysis of DRD2 gene polymorphisms with major depressive disorder in the Chinese Han population.

Publications

Genetic distribution and association analysis of DRD2 gene polymorphisms with major depressive disorder in the Chinese Han population.

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