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Lipoprotein(a) level and MIF gene variant predict incident metabolic syndrome and mortality

Altan Onat, Günay Can, Neslihan Çoban, İbrahim Dönmez, Hakan Çakır, Evin Ademoğlu, Nihan Erginel-Ünaltuna, Hüsniye Yüksel
DOI: 10.1136/jim-2015-000003 Published 28 January 2016
Altan Onat
1Department of Cardiology, Istanbul University, Istanbul, Turkey
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Günay Can
2Department of Public Health, Cerrahpaşa Medical Faculty, Istanbul University, Istanbul, Turkey
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Neslihan Çoban
3Department of Genetics, Institute for Experimental Medical Research, Istanbul University, Istanbul, Turkey
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İbrahim Dönmez
4Department of Cardiology, Izzet Baysal University, Abant, Istanbul, Turkey
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Hakan Çakır
5Darıca Farabi State Hospital, Istanbul, Turkey
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Evin Ademoğlu
6Department of Biochemistry, Medical Faculty, Istanbul University, Istanbul, Turkey
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Nihan Erginel-Ünaltuna
3Department of Genetics, Institute for Experimental Medical Research, Istanbul University, Istanbul, Turkey
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Hüsniye Yüksel
1Department of Cardiology, Istanbul University, Istanbul, Turkey
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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.

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Vol 64 Issue 2 Table of Contents
Journal of Investigative Medicine: 64 (2)
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Lipoprotein(a) level and MIF gene variant predict incident metabolic syndrome and mortality
Altan Onat, Günay Can, Neslihan Çoban, İbrahim Dönmez, Hakan Çakır, Evin Ademoğlu, Nihan Erginel-Ünaltuna, Hüsniye Yüksel
Journal of Investigative Medicine Feb 2016, 64 (2) 392-399; DOI: 10.1136/jim-2015-000003

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Lipoprotein(a) level and MIF gene variant predict incident metabolic syndrome and mortality
Altan Onat, Günay Can, Neslihan Çoban, İbrahim Dönmez, Hakan Çakır, Evin Ademoğlu, Nihan Erginel-Ünaltuna, Hüsniye Yüksel
Journal of Investigative Medicine Feb 2016, 64 (2) 392-399; DOI: 10.1136/jim-2015-000003
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Lipoprotein(a) level and MIF gene variant predict incident metabolic syndrome and mortality
Altan Onat, Günay Can, Neslihan Çoban, İbrahim Dönmez, Hakan Çakır, Evin Ademoğlu, Nihan Erginel-Ünaltuna, Hüsniye Yüksel
Journal of Investigative Medicine Feb 2016, 64 (2) 392-399; DOI: 10.1136/jim-2015-000003
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