LRP5 in premature adrenarche and in metabolic characteristics of prepubertal children.
OBJECTIVE
Premature adrenarche (PA) is associated with unfavourable metabolic characteristics. We hypothesized that genetic variation in low density lipoprotein (LDL) receptor-related protein 5 (LRP5), which is involved in Wnt signalling in the adrenal cortex and in cholesterol metabolism, plays a role in the pathogenesis of PA.


METHODS
We performed a cross-sectional association study in 73 Finnish children with PA and 97 age- and gender-matched healthy controls.


METHODS
LRP5 genotypes were determined by direct sequencing. Single-marker associations with clinical-metabolic characteristics, including adrenocortical function, glucose tolerance and lipid profile, were examined with age and gender as covariates.


RESULTS
Nineteen single nucleotide polymorphisms (SNPs) in LRP5 were found in the 170 children. No significant differences in the genotype distributions were observed between the PA and control groups. SNPs A1330V and N740N were associated with higher serum dehydroepiandrosterone sulphate (DHEAS) levels in the control subjects (A/A vs. A/a; mean 0.8 vs. 1.4 micromol/l, P = 0.01). They were also associated with higher plasma levels of total (4.2 vs. 4.7 mmol/l, P = 0.02) and LDL cholesterol (2.4 vs. 2.9 mmol/l, P = 0.02) in the control group, as was SNP V1119V (P = 0.04 and P = 0.03, respectively). SNPs F549F and V1119V were associated with higher systolic blood pressure (P = 0.04 and P = 0.02, respectively). There were no differences in the parameters of glucose metabolism between the genotype groups.


CONCLUSIONS
Genetic variation in LRP5 did not predispose to PA but was associated with metabolic characteristics, especially lipid profile, in healthy prepubertal children.
Lappalainen
Saila
S
Department of Paediatrics, Kuopio University and University Hospital, Kuopio, Finland. saila.lappalainen@uku.fi
Saarinen
Anne
A
Utriainen
Pauliina
P
Voutilainen
Raimo
R
Jääskeläinen
Jarmo
J
Mäkitie
Outi
O
D050499:Adrenarche / Q000235:genetics* / Q000378:metabolism*; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D005387:Finland; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D008055:Lipids / Q000097:blood; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D008297:Male; D024821:Metabolic Syndrome / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism
D026502:LDL-Receptor Related Proteins; C555482:LRP5 protein, human; D008055:Lipids; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D051153:Wnt Proteins