CDKAL1-related single nucleotide polymorphisms are associated with insulin resistance in a cross-sectional cohort of Greek children.
Five novel loci recently found to be associated with body mass in two GWAS of East Asian populations were evaluated in two cohorts of Swedish and Greek children and adolescents. These loci are located within, or in the proximity of: CDKAL1, PCSK1, GP2, PAX6 and KLF9. No association with body mass has previously been reported for these loci in GWAS performed on European populations. The single nucleotide polymorphisms (SNPs) with the strongest association at each loci in the East Asian GWAS were genotyped in two cohorts, one obesity case control cohort of Swedish children and adolescents consisting of 496 cases and 520 controls and one cross-sectional cohort of 2293 nine-to-thirteen year old Greek children and adolescents. SNPs were surveyed for association with body mass and other phenotypic traits commonly associated with obesity, including adipose tissue distribution, insulin resistance and daily caloric intake. No association with body mass was found in either cohort. However, among the Greek children, association with insulin resistance could be observed for the two CDKAL1-related SNPs: rs9356744 (β = 0.018, p = 0.014) and rs2206734 (β = 0.024, p = 0.001). CDKAL1-related variants have previously been associated with type 2 diabetes and insulin response. This study reports association of CDKAL1-related SNPs with insulin resistance, a clinical marker related to type 2 diabetes in a cross-sectional cohort of Greek children and adolescents of European descent.
Department of Neuroscience, Functional Pharmacology, Uppsala University, BMC, Uppsala, Sweden.
Mathias
M
Rask-Andersen
Department of Neuroscience, Functional Pharmacology, Uppsala University, BMC, Uppsala, Sweden.
Gaëtan
G
Philippot
Department of Nutrition and Dietetics, Harokopio University, Athens, Greece.
George
G
Moschonis
Department of Nutrition and Dietetics, Harokopio University, Athens, Greece.
George
G
Dedoussis
Department of Nutrition and Dietetics, Harokopio University, Athens, Greece.
Yannis
Y
Manios
Department for Clinical Science, Intervention and Technology, Karolinska Institutet, Division of Pediatrics, National Childhood Obesity Centre, Stockholm, Sweden.
Claude
C
Marcus
Department of Neuroscience, Functional Pharmacology, Uppsala University, BMC, Uppsala, Sweden.
Robert
R
Fredriksson
Department of Neuroscience, Functional Pharmacology, Uppsala University, BMC, Uppsala, Sweden.
Helgi B
HB
Schiöth
D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D003430:Cross-Sectional Studies; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D002149:Energy Intake / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D006115:Greece; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D013548:Sweden; D012359:tRNA Methyltransferases
D005819:Genetic Markers; D012359:tRNA Methyltransferases; D051360:Cyclin-Dependent Kinase 5; C525110:CDKAL1 protein, human