PT  - JOURNAL ARTICLE
AU  - Bai, F
AU  - Rankinen, T
AU  - Charbonneau, C
AU  - Belsham, D D
AU  - Rao, D C
AU  - Bouchard, C
AU  - Argyropoulos, G
TI  - Functional dimorphism of two hAgRP promoter SNPs in linkage disequilibrium
AID  - 10.1136/jmg.2003.014092
DP  - 2004 May 01
TA  - Journal of Medical Genetics
PG  - 350--353
VI  - 41
IP  - 5
4099  - http://jmg.bmj.com/content/41/5/350.short
4100  - http://jmg.bmj.com/content/41/5/350.full
SO  - J Med Genet2004 May 01; 41
AB  - The agouti related protein (AgRP) exerts its anabolic effects on food intake by antagonising the alpha-melanocyte stimulating hormone (α-MSH) at its receptors, melanocortin receptors 3 and 4 (MC3R and MC4R). A single nucleotide polymorphism (SNP) in the promoter of the human AgRP (hAgRP), −38C>T, was associated with low body fatness. The −38T allele that was associated with low body fatness also resulted in lower promoter activity. Here we report a novel SNP, −3019G>A, again in the promoter of hAgRP, which is in complete linkage disequilibrium (LD) with the −38C>T SNP (linked alleles: −3019A/−38T and −3019G/−38C). Functional analyses in a human adrenal and two mouse hypothalamus cell lines showed that the −3019A allele had significantly higher promoter activity. Hence, the two linked alleles (−3019A and −38T) had opposite effects on promoter function and yet they were both associated with low body fatness. The region encompassing the −38C>T SNP had approximately 1000-fold higher activity than the region encompassing the −3019G>A SNP, potentially determining the net functional effect between these two SNPs.