title: C-reactive protein gene variants: independent association with late-life depression and circulating protein levels.
abstract: C-reactive protein (CRP) is a heritable biomarker of systemic inflammation that is commonly elevated in depressed patients. Variants in the CRP gene that influence protein levels could thus be associated with depression but this has seldom been examined, especially in the elderly. Depression was assessed in 990 people aged at least 65 years as part of the ESPRIT study. A clinical level of depression (DEP) was defined as having a score of ⩾16 on The Center for Epidemiologic Studies Depression scale or a diagnosis of current major depression based on the Mini-International Neuropsychiatric Interview and according to Diagnostic and Statistical Manual of Mental Disorders-IV criteria. Five single-nucleotide polymorphisms spanning the CRP gene were genotyped, and circulating levels of high-sensitivity CRP were determined. Multivariable analyses adjusted for socio-demographic characteristics, smoking, ischemic pathologies, cognitive impairment and inflammation-related chronic pathologies. The minor alleles of rs1130864 and rs1417938 were associated with a decreased risk of depression in women at Bonferroni-corrected significance levels (P=0.002). CRP gene variants were associated with serum levels in a gender-specific manner, but only rs1205 was found to be nominally associated with both an increased risk of DEP and lower circulating CRP levels in women. Variants of the CRP gene thus influence circulating CRP levels and appear as independent susceptibility factors for late-life depression.
authors.affiliation: 1] Inserm, U1061, Hopital La Colombiere, Montpellier, France [2] Université Montpellier 1, U1061, Montpellier, France.
authors.forename: M-L
authors.initials: ML
authors.lastname: Ancelin
authors.affiliation: 1] Inserm, U1061, Hopital La Colombiere, Montpellier, France [2] Université Montpellier 1, U1061, Montpellier, France.
authors.forename: A
authors.initials: A
authors.lastname: Farré
authors.affiliation: 1] Inserm, U1061, Hopital La Colombiere, Montpellier, France [2] Université Montpellier 1, U1061, Montpellier, France.
authors.forename: I
authors.initials: I
authors.lastname: Carrière
authors.affiliation: 1] Inserm, U1061, Hopital La Colombiere, Montpellier, France [2] Université Montpellier 1, U1061, Montpellier, France [3] Faculty of Medicine, Imperial College, London, UK.
authors.forename: K
authors.initials: K
authors.lastname: Ritchie
authors.affiliation: 1] Inserm, U1061, Hopital La Colombiere, Montpellier, France [2] Université Montpellier 1, U1061, Montpellier, France.
authors.forename: I
authors.initials: I
authors.lastname: Chaudieu
authors.affiliation: 1] Inserm, U1061, Hopital La Colombiere, Montpellier, France [2] Université Montpellier 1, U1061, Montpellier, France [3] Disease Epigenetics Group, Murdoch Children's Research Institute, Parkville, VIC, Australia [4] Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Ryan
mesh_terms: D000367:Age Factors; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000235:genetics* / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide
chemical_list: D000928:Antidepressive Agents; D002097:C-Reactive Protein