Dataset Information

Sequence polymorphisms of MC1R gene and their association with depression and antidepressant response.

ABSTRACT:

Objective

Melanocortin 1 receptor (MC1R) is involved in various functions, such as pigmentation, antipyretic and anti-inflammatory actions, development of melanoma, susceptibility to ultraviolet-induced sun damage, modification of oculocutaneous albinism, development of freckles, and mediation of female-specific mechanisms of analgesia. MC1R's natural agonists include α-melanocyte-stimulating hormone and corticotrophin (ACTH1-39), which are important components of hypothalamic pituitary adrenal axis and increase in response to stress. Given the multiple relevant roles of MC1R, we studied whether the MC1R gene would be associated with susceptibility to major depressive disorder or with response to antidepressant treatment.

Methods

The human MC1R gene is highly polymorphic; therefore, we sequenced the entire MC1R coding region of 1122 bp in 181 depressed Mexican-American patients and 185 Mexican-American controls.

Results

A total of 23 single nucleotide polymorphisms (SNPs, 15 known and eight new) were found within the sequenced region. Among the common SNPs, the nonsynonymous SNP, rs885479 (R163Q) was associated with the diagnosis of depression (P=0.04). The nonsynonymous SNP, rs2228479 (V92M) and the synonymous SNP, rs2228478 were found to be associated with the remission with desipramine treatment. No associations were found for remission with fluoxetine treatment or for the combined sample treated with fluoxetine or desipramine. The frequency of one (H2) of the five haplotypes identified was higher in depressed patients when compared with controls (P=0.05). In-silico functional analysis indicates that SNPs rs885479 and rs2228479 have significant impact on the protein function.

Conclusion

The MC1R gene might be associated with major depressive disorder and with treatment response to desipramine.

SUBMITTER: Wu GS

PROVIDER: S-EPMC9531708 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Publications

Sequence polymorphisms of MC1R gene and their association with depression and antidepressant response.

Wu Gui-Sheng GS Luo Huai-Rong HR Dong Chuanhui C Mastronardi Claudio C Licinio Julio J Wong Ma-Li ML

Psychiatric genetics 20110201 1

<h4>Objective</h4>Melanocortin 1 receptor (MC1R) is involved in various functions, such as pigmentation, antipyretic and anti-inflammatory actions, development of melanoma, susceptibility to ultraviolet-induced sun damage, modification of oculocutaneous albinism, development of freckles, and mediation of female-specific mechanisms of analgesia. MC1R's natural agonists include α-melanocyte-stimulating hormone and corticotrophin (ACTH1-39), which are important components of hypothalamic pituitary ...[more]

PMID: 21052032

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Project description:The "antidepressant efficacy" survey (AES) was deployed to > 50,000 23andMe, Inc. research participants to investigate the genetic basis of treatment-resistant depression (TRD) and non-treatment-resistant depression (NTRD). Genome-wide association studies (GWAS) were performed, including TRD vs. NTRD, selective serotonin reuptake inhibitor (SSRI) responders vs. non-responders, serotonin-norepinephrine reuptake inhibitor (SNRI) responders vs. non-responders, and norepinephrine-dopamine reuptake inhibitor responders vs. non-responders. Only the SSRI association reached the genome-wide significance threshold (p < 5 × 10-8): one genomic region in RNF219-AS1 (SNP rs4884091, p = 2.42 × 10-8, OR = 1.21); this association was also observed in the meta-analysis (13,130 responders vs. 6,610 non-responders) of AES and an earlier "antidepressant efficacy and side effects" survey (AESES) cohort. Meta-analysis for SNRI response phenotype derived from AES and AESES (4030 responders vs. 3049 non-responders) identified another genomic region (lead SNP rs4955665, p = 1.62 × 10-9, OR = 1.25) in an intronic region of MECOM passing the genome-wide significance threshold. Meta-analysis for the TRD phenotype (31,068 NTRD vs 5,714 TRD) identified one additional genomic region (lead SNP rs150245813, p = 8.07 × 10-9, OR = 0.80) in 10p11.1 passing the genome-wide significance threshold. A stronger association for rs150245813 was observed in current study (p = 7.35 × 10-7, OR = 0.79) than the previous study (p = 1.40 × 10-3, OR = 0.81), and for rs4955665, a stronger association in previous study (p = 1.21 × 10-6, OR = 1.27) than the current study (p = 2.64 × 10-4, OR = 1.21). In total, three novel loci associated with SSRI or SNRI (responders vs. non-responders), and NTRD vs TRD were identified; gene level association and gene set enrichment analyses implicate enrichment of genes involved in immune process.

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Dataset Information

Sequence polymorphisms of MC1R gene and their association with depression and antidepressant response.

Objective

Methods

Results

Conclusion

Publications

Sequence polymorphisms of MC1R gene and their association with depression and antidepressant response.

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