Functional dimorphism of two hAgRP promoter SNPs in linkage disequilibrium

F. Bai, T. Rankinen, C. Charbonneau, D. D. Belsham, D. C. Rao, C. Bouchard, G. Argyropoulos

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18 Scopus citations

Abstract

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 alteles: -3019A/-387 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 -387) 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.

Original languageEnglish
Pages (from-to)350-353
Number of pages4
JournalJournal of Medical Genetics
Volume41
Issue number5
StatePublished - May 1 2004

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    Bai, F., Rankinen, T., Charbonneau, C., Belsham, D. D., Rao, D. C., Bouchard, C., & Argyropoulos, G. (2004). Functional dimorphism of two hAgRP promoter SNPs in linkage disequilibrium. Journal of Medical Genetics, 41(5), 350-353.