The insulin gene variable number of tandem repeat: associations and interactions with childhood body fat mass and insulin secretion in normal children.
BACKGROUND
Polymorphism at the insulin gene (INS) variable number of tandem repeat (VNTR) shows variable associations with childhood body mass index (BMI) in different populations.


OBJECTIVE
The objective of this study was to observe INS VNTR associations with body composition and insulin secretion in children.


METHODS
The study was designed as a prospective birth cohort study.


METHODS
A total of 947 children genotyped for the INS VNTR participated.


METHODS
Main outcome measures were whole body dual x-ray emission absorptiometry at 9 yr to estimate height-corrected fat mass index (FMI), truncal FMI, and fat-free mass, and insulin secretion after oral glucose at 8 yr.


RESULTS
Homozygous III/III children had higher BMI (P = 0.020), FMI (P = 0.015), and truncal FMI (P = 0.022) at 9 yr than class I bearers, but no difference in fat-free mass (P = 0.23). Gain in weight sd score between birth and 3 yr was associated positively with BMI, FMI, and truncal FMI in class I bearers, but not in III/III children (p-interaction with genotype = 0.009-0.066). INS VNTR genotype was not associated overall with insulin secretion at 8 yr (P = 0.64), but class I bearers showed a stronger positive correlation between insulin secretion and BMI at 8 yr (regression coefficient +/- se, 0.26 +/- 0.05; P < 0.0001) than III/III children (-0.10 +/- 0.07; P = 0.48) (p-interaction = 0.003).


CONCLUSIONS
We clarified that the overall association between INS VNTR class III/III genotype and larger BMI in this population relates to fat mass, but not fat-free mass. In contrast, among the subgroup of children who showed rapid infancy weight gain, class I bearers tended to have larger BMI and fat mass than III/III children. This genetic interaction could relate to insulin secretion, which, in class I bearers, increased more rapidly with overweight and obesity.
Heude
Barbara
B
Medical Research Council Epidemiology Unit, Strangeways Research Laboratory, Wort's Causeway, Cambridge CB1 8RN, United Kingdom.
Petry
Clive J
CJ
Pembrey
Marcus
M
Dunger
David B
DB
Ong
Ken K
KK
D001823:Body Composition; D015992:Body Mass Index; D049628:Body Size; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005215:Fasting; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D007328:Insulin / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D018598:Minisatellite Repeats / Q000235:genetics*; D009765:Obesity / Q000235:genetics; D011446:Prospective Studies; D015430:Weight Gain
D007328:Insulin