title: Lipoprotein(a) level and MIF gene variant predict incident metabolic syndrome and mortality.
abstract: Owing to the scarcity of available information, we aimed to assess the association of migration inhibitory factor (MIF)-173 G/C genotypes and serum lipoprotein(Lp)(a) with incident metabolic syndrome (MetS) and all-cause mortality, respectively. In population based, middle-aged adults (n=1297), stratified by gender and presence of MetS, we used Lp(a) quintiles to identify non-linear associations with outcomes using Cox regression models, adjusted for MIF genotype, age, smoking status, high density lipoprotein cholesterol, and systolic blood pressure. After 5.2 years of follow-up, 151 cases of incident MetS and 123 deaths were recorded. For incident MetS, adjusted HRs increased in each gender across four declining quintiles, starting from the highest quintile in men and from quintile 4 in women. The MIF CC-GC genotype appeared to contribute to the risk estimates in men. Similarly adjusted models in the whole sample disclosed that all-cause mortality tended to be inversely associated with Lp(a) quintiles and yielded an HR (2.42 (95% CI 1.03 to 5.81)) in men in quintile 2, whereas the MIF genotype additively predicted mortality (HR 1.79 (95% CI 1.01 to 3.18)) only in men. Excess risk of death was additively conferred on Turkish men by the MIF CC-GC genotype and by apparently reduced circulating Lp(a) assays, supporting the notion that 'low' serum Lp(a), mediating autoimmune activation, is a major determinant of metabolic disease risk and death. Damaged MIF protein and more complex autoimmune activation in women may be responsible from lack of relationship to MetS/mortality.
authors.affiliation: Department of Cardiology, Istanbul University, Istanbul, Turkey.
authors.forename: Altan
authors.initials: A
authors.lastname: Onat
authors.affiliation: Department of Public Health, Cerrahpaşa Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Günay
authors.initials: G
authors.lastname: Can
authors.affiliation: Department of Genetics, Institute for Experimental Medical Research, Istanbul University, Istanbul, Turkey.
authors.forename: Neslihan
authors.initials: N
authors.lastname: Çoban
authors.affiliation: Department of Cardiology, Izzet Baysal University, Abant, Istanbul, Turkey.
authors.forename: İbrahim
authors.initials: İ
authors.lastname: Dönmez
authors.affiliation: Darıca Farabi State Hospital, Istanbul, Turkey.
authors.forename: Hakan
authors.initials: H
authors.lastname: Çakır
authors.affiliation: Department of Biochemistry, Medical Faculty, Istanbul University, Istanbul, Turkey.
authors.forename: Evin
authors.initials: E
authors.lastname: Ademoğlu
authors.affiliation: Department of Genetics, Institute for Experimental Medical Research, Istanbul University, Istanbul, Turkey.
authors.forename: Nihan
authors.initials: N
authors.lastname: Erginel-Ünaltuna
authors.affiliation: Department of Cardiology, Istanbul University, Istanbul, Turkey.
authors.forename: Hüsniye
authors.initials: H
authors.lastname: Yüksel
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D015994:Incidence; D019746:Intramolecular Oxidoreductases / Q000235:genetics*; D017270:Lipoprotein(a) / Q000097:blood*; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000235:genetics* / Q000401:mortality*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016016:Proportional Hazards Models
chemical_list: D017270:Lipoprotein(a); D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human
keywords: Autoimmunity; Death; Lipoproteins; Macrophages