Agouti-related protein promoter variant associated with leanness and decreased risk for diabetes in West Africans.
OBJECTIVE
The role of the central melanocortin system in the development of obesity has been extensively studied. Single-nucleotide polymorphisms (SNPs) within several candidate genes have been associated with food intake and obesity-related phenotypes; however, few of these associations have been replicated. SNPs in the agouti-related protein (AGRP) gene coding (Ala67Thr, 199G/A) and promoter (-38C/T) have been reported to be associated with body mass index (BMI), fat mass (FM) and percent body fat, in populations of European and African descent. In this study, we evaluated the association between the functional AGRP -38C/T promoter SNP and weight-related traits, namely BMI, FM and fat-free mass (FFM), as well as diabetes status.


METHODS
An association study of the AGRP -38C/T SNP and indices of obesity and diabetes status.


METHODS
A well-characterized population of 538 West Africans from Ghana and Nigeria recruited in the AADM (Africa America Diabetes Mellitus) study (mean age 52 years, 41.3% males, 71% diabetic).


METHODS
Genotyping of the AGRP -38C/T SNP, BMI, FM, FFM and fasting plasma glucose.


RESULTS
Women carrying two copies of the variant T allele had significantly lower BMI (OR=0.47; 95% CI, 0.25-0.87). Also, men with at least one copy of the variant T allele were over two times less likely to be diabetic than other men (OR=0.44; 95% CI, 0.22-0.89).


CONCLUSIONS
Our results replicate previous findings and implicate the AGRP -38C/T SNP in the regulation of body weight in West Africans.
Bonilla
C
C
National Human Genome Center at Howard University, Washington, DC, USA.
Panguluri
R K
RK
Taliaferro-Smith
L
L
Argyropoulos
G
G
Chen
G
G
Adeyemo
A A
AA
Amoah
A
A
Owusu
S
S
Acheampong
J
J
Agyenim-Boateng
K
K
Eghan
B A
BA
Oli
J
J
Okafor
G
G
Abbiyesuku
F
F
Johnson
T
T
Rufus
T
T
Fasanmade
O
O
Chen
Y
Y
Collins
F S
FS
Dunston
G M
GM
Rotimi
C
C
Kittles
R A
RA
D054366:Agouti Signaling Protein; D054369:Agouti-Related Protein; D044383:Black People / Q000235:genetics*; D001786:Blood Glucose / Q000235:genetics; D050218:Body Fat Distribution; D015992:Body Mass Index; D001835:Body Weight; D003920:Diabetes Mellitus / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012737:Sex Factors
C515198:AGRP protein, human; D054366:Agouti Signaling Protein; D054369:Agouti-Related Protein; D001786:Blood Glucose; D036341:Intercellular Signaling Peptides and Proteins