Smart, MC and Dedoussis, G and Yiannakouris, N and Grisoni, ML and Dror, GK and Yannakoulia, M and Papoutsakis, C and Louizou, E and Mantzoros, CS and Melistas, L and Kontogianni, MD and Cooper, JA and Humphries, SE and Talmud, PJ and EARSII Consortium, (2011) Genetic variation within IL18 is associated with insulin levels, insulin resistance and postprandial measures. NUTR METAB CARDIOVAS , 21 (7) 476 - 484. 10.1016/j.numecd.2009.12.004.
Background and aims: IL-18 expression is up-regulated in atherosclerotic plaques, and higher levels are seen in obese and Type 2 Diabetic individuals. More recently, a possible role for IL-18 in glucose and energy homeostasis has been suggested.Methods and results: We investigated variation within the IL18 gene and its association with measures of obesity and the metabolic syndrome. Five IL18 tagging single nucleotide polymorphisms (rs1946519, rs2043055, rs549908, rs360729, rs3882891) were selected and genotyped in the Gene-Diet Attica Investigation on childhood obesity (GENDAI) (age range 10-14 yrs); in young European men in the second European Atherosclerosis Research offspring Study (EARSII), an offspring study (age range 18-28 yrs) and in a group of healthy women from the Greek Obese Women study (GrOW) (age range 18-74 yrs). Six common haplotypes were observed. In GrOW, Hap6 (Frequency-2.6%) was associated with higher insulin levels (p < 0.0001), estimates of HOMA(-Insulin Resistance) (p < 0.0001) and HOMA(-beta-cell) (p < 0.0001) compared to the common haplotype Hap1 (Frequency-33.2%). In EARSII, rs2043055 was associated with peak and area under the curve triglycerides (p = 0.001 and p = 0.002, respectively) after an oral fat tolerance test in 'cases' but not 'controls'. None of the haplotypes were associated with measures of body fatness in any of the studies.Conclusion: Association of IL18 variation with insulin levels and estimates of insulin resistance were only observed in our adult study, suggesting that the effects of IL-18 are only associated with increasing age. Taken together with the association of IL18 variants with post-prandial measures, this provides support for IL-18 as a metabolic factor. (C) 2010 Elsevier B. V. All rights reserved.
|Title:||Genetic variation within IL18 is associated with insulin levels, insulin resistance and postprandial measures|
|Open access status:||An open access publication|
|Keywords:||Interleukin 18, Obesity, Insulin resistance, Single nucleotide polymorphisms, Genetic variants, Haplotypes, CORONARY-HEART-DISEASE, HOMEOSTASIS MODEL ASSESSMENT, METABOLIC SYNDROME, HUMAN ADIPOCYTES, ADIPOSE-TISSUE, INTERLEUKIN-18, OBESITY, PLASMA, INFLAMMATION, HAPLOTYPE|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science|
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