A gender-specific COMT haplotype contributes to risk modulation rather than disease severity of major depressive disorder in a Chinese population.
J Affect Disord
; 246: 376-386, 2019 03 01.
Article
em En
| MEDLINE
| ID: mdl-30597299
ABSTRACT
BACKGROUND:
COMT rs4680 Val158 allele is associated with high MB-COMT protein expression and elevated activity compared to the Met158 allele in post-mortem brains. A meta-analysis study suggested the link between COMT SNPs and MDD risk; in addition, MB membrane-bound (MB-COMT) specific genetic variation was reported that influences predisposition to depression amongst females.METHODS:
Four tagSNPs, including rs4680, were genotyped. 268 MDD subjects and 223 controls were enrolled. MDD severity was rated by HDRS. Total-COMT and MB-COMT mRNA were detected by quantitative PCR. COMT protein and activity were assayed by western blot and methyltransferase assay, respectively.RESULTS:
Haplotype TG of rs4633-rs4680, rs4646312 C, and rs4633 T allele might be linked to MDD vulnerability. Haplotype TG may interact with gender and affect MDD risk, since female haplotype TG carriers were estimated for a 9.17-fold higher risk than counterparts. COMT SNPs were not associated with HDRS scores. Haplotype TG female controls had higher MB-COMT protein, whereas non-TG female controls had higher soluble cytoplasmic (S-COMT) protein than other groups. COMT activity was much higher in controls than in MDD subjects.LIMITATIONS:
Restricted numbers of homozygous TG carriers were recruited and analyzed for COMT mRNA, protein and activity. Only peripheral blood samples were used.CONCLUSIONS:
A female-specific haplotype (haplotype TG)-MDD vulnerability association was found. TG female controls had higher MB-COMT protein and S-COMT. Altogether, high COMT protein and activity in female TG controls may be predisposing factors for enhanced MDD risk, though not correlated to MDD severity as rated by HDRS.
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Base de dados:
MEDLINE
Assunto principal:
Haplótipos
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Catecol O-Metiltransferase
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Predisposição Genética para Doença
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Transtorno Depressivo Maior
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Genótipo
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article