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


CONCLUSIONS
The MC1R gene might be associated with major depressive disorder and with treatment response to desipramine.
Center for Drug Screening and Research, State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, The Chinese Academy of Sciences, Yunnan, China.
Gui-Sheng
GS
Wu
Huai-Rong
HR
Luo
Chuanhui
C
Dong
Claudio
C
Mastronardi
Julio
J
Licinio
Ma-Li
ML
Wong
D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001483:Base Sequence; D003863:Depression / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D017058:Mexican Americans / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D012074:Remission Induction
D000928:Antidepressive Agents; D044102:Receptor, Melanocortin, Type 1