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Abstract: 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-β-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. [Copyright &y& Elsevier]

Abstract: Background and aims: Studies have consistently demonstrated that variants in a number of candidate genes are significant determinants of lipid levels in adults. However, few studies have investigated the impact of these variants in children. Therefore, in the present investigation we examined the influence of ten common variants in the genes for lipoprotein lipase (LPL – S447X), cholesterol ester transfer protein (CETP –Taq1B) apolipoprotein (APO) E (ɛ2, ɛ3, ɛ4), APOA5 (−1131C>T and S19W), APOA4 (S347T) and APOC3 (−482C>T; 1100C>T and 3238G>C) on lipoprotein levels children from the Gene–Diet Attica Investigation on childhood obesity (GENDAI). Methods and results: The ten variants selected were genotyped in 882 Greek children, mean age: 11.2±0.7 years (418 females and 464 males). Genotypes were assessed using TaqMan technology. Significantly higher total cholesterol (TC) (p =0.0001) and low-density lipoprotein cholesterol (LDL-C) (p <0.0001) were observed in APOE ɛ4 carriers compared to ɛ3/ɛ3 homozygotes and ɛ2 carriers. The association of APOE genotype with TC and high-density lipoprotein cholesterol (HDL-C) ratio (p =0.0008) was further modulated by body mass index. Carriers of the CETP TaqIB B2 allele had significantly higher HDL-C (p <0.0001) and significantly lower TC: HDL-C ratio (p <0.0001) compared to B1/B1 individuals. No significant associations were observed between APOA4, APOA5 and APOC3 variants and serum lipids. Conclusion: This study demonstrates that these common variants are associated with lipid levels in this healthy paediatric cohort, suggesting that even in these young children there may be potential in predicting their lifelong exposure to an adverse lipid profile. [Copyright &y& Elsevier]