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Case-control association study of ABCB1 gene and major depressive disorder in a local Chinese Han population.

ABSTRACT: BACKGROUND:Human P-glycoprotein encoded by the ATP-binding cassette sub-family B member 1 (ABCB1) gene is expressed in the blood-brain barrier. ABCB1 protects the brain from many drugs and toxins such as glucocorticoids through the efflux pump. Recent evidence suggests that a specific allele of the ABCB1 gene confers susceptibility to major depressive disorder (MDD) in the Japanese population. The aim of this study was to explore the association of ABCB1 gene polymorphisms with MDD in a local Chinese Han population. METHODS:Two hundred and ninety-two MDD patients and 208 unrelated individuals were matched by age and sex and examined using a case-control design. Six single nucleotide polymorphisms (SNPs) of the ABCB1 gene, including rs1045642, rs2032583, rs2032582, rs2235040, rs1128503, and rs2235015, were genotyped by ligase detection reaction and multiplex polymerase chain reaction. Linkage disequilibrium and haplotype analysis were investigated in the two study groups. RESULTS:Significant protection for MDD individuals carrying the TG haplotype of rs1045642-rs2032582 was observed (odds ratio 0.470, 95% confidence interval 0.251-0.897, P=0.01). The rs2032582 (G2677T) and rs1128503 (C1236T) SNPs of ABCB1 showed nominal associations with MDD; the other four SNPs of the ABCB1 gene were not associated with MDD. CONCLUSION:Chinese individuals carrying the TG haplotype of rs1045642-rs2032582 had a nearly 53% lower risk of developing MDD. To the best of our knowledge, this is the first report to analyze the effect of ABCB1 polymorphism on the risk of MDD in a Chinese population.

SUBMITTER: Xie WW

PROVIDER: S-EPMC4531014 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Case-control association study of ABCB1 gene and major depressive disorder in a local Chinese Han population.

Xie Wei-Wei WW Zhang Lin L Wu Ren-Rong RR Yu Yan Y Zhao Jing-Ping JP Li Le-Hua LH

Neuropsychiatric disease and treatment 20150804

<h4>Background</h4>Human P-glycoprotein encoded by the ATP-binding cassette sub-family B member 1 (ABCB1) gene is expressed in the blood-brain barrier. ABCB1 protects the brain from many drugs and toxins such as glucocorticoids through the efflux pump. Recent evidence suggests that a specific allele of the ABCB1 gene confers susceptibility to major depressive disorder (MDD) in the Japanese population. The aim of this study was to explore the association of ABCB1 gene polymorphisms with MDD in a ...[more]

PMID: 26347319

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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

Case-control association study of ABCB1 gene and major depressive disorder in a local Chinese Han population.

Publications

Case-control association study of ABCB1 gene and major depressive disorder in a local Chinese Han population.

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