Variations in human HM74 (GPR109B) and HM74A (GPR109A) niacin receptors.

Article Details

Citation

Zellner C, Pullinger CR, Aouizerat BE, Frost PH, Kwok PY, Malloy MJ, Kane JP

Variations in human HM74 (GPR109B) and HM74A (GPR109A) niacin receptors.

Hum Mutat. 2005 Jan;25(1):18-21.

PubMed ID
15580557 [ View in PubMed
]
Abstract

HM74 (GPR109B) and the highly homologous gene, HM74A (GPR109A) code for Gi-G protein-coupled orphan receptors that recently have been discovered to be involved in the metabolic effects of niacin. The B vitamin niacin is an important agent used in the treatment of dyslipidemias, but its use is limited by side effects. The novel role of the adjacent HM74 and HM74A genes in the metabolism of niacin may provide new targets for drug development. Human genetic variations in HM74 and HM74A have been reported but have not been studied in detail. These variations may play a role in the response to agents targeting receptors coded by these genes. Here we show that many of the nonsynonymous SNPs listed in public databases for HM74 and HM74A are artifacts resulting from extensive homology between these two genes. This may be representative of a neglected phenomenon in reporting sequences of highly homologous genes. We provide primer sequences that permit selective amplification of the complete coding regions of HM74 and HM74A. Using these primers, we show that subsequent sequencing of HM74 and HM74A reveals a novel and unique variation in the HM74A gene. Haplotype analysis suggests four SNPs can define the five major haplotypes that lie within a single haplotype block encompassing these two genes.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
Inositol nicotinateHydroxycarboxylic acid receptor 2ProteinHumans
Yes
Agonist
Details
Inositol nicotinateHydroxycarboxylic acid receptor 3ProteinHumans
Yes
Agonist
Details
NiacinHydroxycarboxylic acid receptor 2ProteinHumans
Yes
Agonist
Details