Smallness for gestational age interacts with high mobility group A2 gene genetic variation to modulate height.
OBJECTIVE
Height variability is largely under genetic control, although identifying the genetic variants involved has been until recently challenging. Smallness for gestational age (SGA) is a risk factor for adult short stature. Genome-wide association studies have identified a single nucleotide polymorphism (SNP) (rs1042725) in the high mobility group A2 gene (HMGA2) that consistently associates with height variability but its interaction with SGA is unknown.


METHODS
We assess the contribution of rs1042725 SNP and height variability in a French population and the impact of rs1042725 on SGA status at birth and height at adulthood in SGA individuals.


METHODS
We genotyped rs1042725 in 4710 healthy participants from the Data from an Epidemiological Study on the Insulin Resistance syndrome (DESIR) cohort, 743 normal birth weight and 660 SGA individuals from the Haguenau study.


RESULTS
rs1042725 is associated with increased height in the cohort participants (0.36 cm 95% CI (0.12-0.61) per C allele, P=0.004) but not with the SGA status or birth length. Interestingly, rs1042725 had a stronger effect on height in SGA participants (0.94 cm 95% CI (0.24-1.64) per C allele, P=0.009), especially in men (1.45 cm 95% CI (0.44-2.46) per C allele, P=0.005) in whom rs1042725 may explain 3% of height variability. SGA men carrying at least one C allele copy experienced more frequent catch-up in height (P(add)=0.07; P(dom)=0.03).


CONCLUSIONS
Our study supports further the contribution of HMGA2 rs1042725 to height variability in European populations and shows an increased effect on height in SGA individuals where this variant favors height catch-up.
Bouatia-Naji
Nabila
N
INSERM, Unité 690, Robert Debré Hospital, Paris F-75019, France.
Marchand
Marion
M
Cavalcanti-Proença
Christine
C
Daghmoun
Samia
S
Durand
Emmanuelle
E
Tichet
Jean
J
Marre
Michel
M
Balkau
Beverley
B
Froguel
Philippe
P
Lévy-Marchal
Claire
C
D000328:Adult; D000368:Aged; D000483:Alleles; D001827:Body Height / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005602:France / Q000453:epidemiology; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D025743:HMGA2 Protein / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age / Q000254:growth & development*; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012727:Sex Characteristics
D025743:HMGA2 Protein