RESUMO
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(-ß-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.
Assuntos
Resistência à Insulina/genética , Insulina/sangue , Interleucina-18/genética , Síndrome Metabólica/genética , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Idoso , Criança , Europa (Continente) , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Grécia , Humanos , Masculino , Síndrome Metabólica/sangue , Pessoa de Meia-Idade , Obesidade/sangue , Período Pós-Prandial , Triglicerídeos/sangue , Adulto JovemRESUMO
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 (epsilon2, epsilon3, epsilon4), 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 epsilon4 carriers compared to epsilon3/epsilon3 homozygotes and epsilon2 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.
Assuntos
Apolipoproteínas E/genética , Proteínas de Transferência de Ésteres de Colesterol/genética , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Colesterol/sangue , Hipercolesterolemia/genética , Lipase Lipoproteica/genética , Apolipoproteína C-III/genética , Apolipoproteínas A/genética , Índice de Massa Corporal , Criança , Colesterol/genética , HDL-Colesterol/genética , LDL-Colesterol/genética , Estudos de Coortes , Feminino , Estudos de Associação Genética , Grécia , Heterozigoto , Homozigoto , Humanos , Hipercolesterolemia/sangue , Masculino , Polimorfismo de Nucleotídeo Único , Estatística como AssuntoRESUMO
BACKGROUND/OBJECTIVES: Height is a classic polygenic trait, with a number of genes underlying its variation. We evaluated the prospect of gene-to-diet interactions in a children's cohort, for the insulin-like growth factor II (IGF) rs680 polymorphism and height variation. SUBJECTS/METHODS: We screened 795 periadolescent children (424 girls) aged 10-11 years old from the Gene and Diet Attica Investigation (GENDAI) pediatric cohort for the IGF rs680 polymorphism (rs680). RESULTS: Children homozygous for the common allele (GG) were taller (148.9+/-7.9 cm) compared with those with the A allele (148.1+/-7.9 cm), after adjusting for age, sex and dairy intake (beta+/-s.e.: 2.1+/-0.95, P=0.026). A trend for rs680 x dairy intake interaction was also revealed (P=0.09). Stratification by IGF rs680 genotype revealed positive significant (P=0.014) association between dairy product intake and height in A-allele children adjusted for the same confounders. A daily increase of four dairy servings was associated with a 0.4 cm increase in height. On grouping dairy intake into low (1.9+/-0.7 servings per day) and high dairy product consumption (4.4+/-1.5 servings per day), children with the A allele who were high dairy product consumers were taller compared with the low dairy product consumers (148.8+/-7.9 vs 147.4+/-7.7 cm, respectively, P=0.05). CONCLUSIONS: A higher consumption of dairy products is associated with increased height depending on the rs680 IGF2 genotype.
