Role of ghrelin polymorphisms in obesity based on three different studies.
OBJECTIVE
Associations between preproghrelin DNA variants and obesity-related phenotypes were studied in 3004 subjects from the Québec Family Study (QFS), the HERITAGE Family Study (HERITAGE), and the Swedish Obese Subjects (SOS) Study.


METHODS
Body mass index (BMI), fat mass (FM) from underwater weighing, and abdominal fat from computerized tomography were measured. The ghrelin polymorphisms were identified by polymerase chain reaction.


RESULTS
Arg51Gln QFS subjects (n = 6) had lower ghrelin concentrations (p = 0.007) than Arg51Arg subjects (n = 14). White preproghrelin Met72Met subjects in HERITAGE had the lowest BMI (p = 0.020), and those in the QFS cohort had the lowest FM (p < 0.001). Met72 carrier status (Met72+) was associated with lower FM (p = 0.026) and higher insulin-like growth factor-1 levels (p = 0.019) among blacks. Met72Met QFS subjects had less visceral fat (p = 0.002) and a lower fasting respiratory quotient (p = 0.037). HERITAGE Met72+ white subjects also showed lower exercise respiratory quotient (p = 0.030) and higher maximal oxygen uptake (p = 0.023). Furthermore, the prevalence of Met72+ was higher (19.2%; p < 0.05) in SOS subjects whose BMI was < or =25 kg/m(2) than in those with BMI >25 kg/m(2) (14.8%). SOS Met72+ obese women had a lower (11.4%; p = 0.032) prevalence of hypertension than noncarriers (23.9%).


CONCLUSIONS
Arg51Gln mutation was associated with lower plasma ghrelin levels but not with obesity. The preproghrelin Met72 carrier status seems to be protective against fat accumulation and associated metabolic comorbidities.
Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana 70808-4124, USA.
Olavi
O
Ukkola
Eric
E
Ravussin
Peter
P
Jacobson
Louis
L
Pérusse
Tuomo
T
Rankinen
Matthias
M
Tschöp
Mark L
ML
Heiman
Arthur S
AS
Leon
D C
DC
Rao
James S
JS
Skinner
Jack H
JH
Wilmore
Lars
L
Sjöström
Claude
C
Bouchard
D000005:Abdomen; D000273:Adipose Tissue; D000483:Alleles; D001823:Body Composition; D015992:Body Mass Index; D015444:Exercise; D005260:Female; D005838:Genotype; D054439:Ghrelin; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000235:genetics; D008297:Male; D009154:Mutation; D009765:Obesity / Q000150:complications / Q000235:genetics*; D010101:Oxygen Consumption; D036361:Peptide Hormones / Q000097:blood / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011792:Quebec; D013548:Sweden; D014057:Tomography, X-Ray Computed
D054439:Ghrelin; D036361:Peptide Hormones