Association of a MTNR1B gene variant with fasting glucose and HOMA-B in children and adolescents with high BMI-SDS.
BACKGROUND
Genome-wide association studies have shown that the melatonin receptor 1B (MTNR1B) gene locus is strongly associated with fasting glucose and β-cell function. However, data are rather limited to the adult population and normal-weight children. So far, little is known whether similar associations are present in overweight and obese children and adolescents.


OBJECTIVE
The aim is to investigate an MTNR1B polymorphism in a sample of 310 overweight and obese children and adolescents (mean body mass index standard deviation score (BMI-SDS)): 2.74 (± 0.55), mean age: 14 (± 2) years), who participated in a short-term weight-loss program based on energy reduction, physical activity, and behavior therapy.


METHODS
We investigated an association between genotype and fasting glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and of β-cell function (HOMA-B), and anthropometric parameters and their change during intervention.


RESULTS
The minor G allele of polymorphism rs10830963 was significantly associated with increased fasting glucose (0.205  mmol/l, P<0.0001) and decreased HOMA-B (-0.353, P < 0.0001). Categorizing the sample into BMI-SDS groups, these significant associations were abolished in children with BMI-SDS below 2.5 but remained in those with higher BMI-SDS values with stronger β-estimates. The P value for the genotype × BMI-SDS category interaction was 0.012 for fasting glucose and 0.083 for HOMA-B. There was no significant association between genotype and anthropometric parameters and their change during intervention.


CONCLUSIONS
This is the first single study, replicating the association between the MTNR1B locus and diabetes-related traits in overweight and obese children and adolescents. The effect sizes in children and adolescents seem to be stronger than in adults and differed among BMI-SDS categories.
Else Kroener-Fresenius-Centre for Nutritional Medicine, University Hospital Klinikum rechts der Isar, Universität München, Munich, Germany. christina.holzapfel@wzw.tum.de
Christina
C
Holzapfel
Monika
M
Siegrist
Melanie
M
Rank
Helmut
H
Langhof
Harald
H
Grallert
Jens
J
Baumert
Corinna
C
Irimie
Norman
N
Klopp
Bernd
B
Wolfarth
Thomas
T
Illig
Hans
H
Hauner
Martin
M
Halle
D000293:Adolescent; D000483:Alleles; D001786:Blood Glucose / Q000235:genetics*; D015992:Body Mass Index; D016009:Chi-Square Distribution; D002648:Child; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D009043:Motor Activity; D009765:Obesity / Q000235:genetics* / Q000628:therapy; D050177:Overweight / Q000235:genetics* / Q000628:therapy; D020641:Polymorphism, Single Nucleotide; D044123:Receptor, Melatonin, MT2 / Q000235:genetics*; D055105:Waist Circumference; D015431:Weight Loss / Q000235:genetics; D055815:Young Adult
D001786:Blood Glucose; D044123:Receptor, Melatonin, MT2