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Variations in human HM74 (GPR109B) and HM74A (GPR109A) niacin receptors.
Hum Mutat. 2005 Jan; 25(1):18-21.HM

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.

Authors+Show Affiliations

Cardiovascular Research Institute, University of California, San Francisco 94143-0130, USA. zellner@medicine.ucsf.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15580557

Citation

Zellner, Christian, et al. "Variations in Human HM74 (GPR109B) and HM74A (GPR109A) Niacin Receptors." Human Mutation, vol. 25, no. 1, 2005, pp. 18-21.
Zellner C, Pullinger CR, Aouizerat BE, et al. Variations in human HM74 (GPR109B) and HM74A (GPR109A) niacin receptors. Hum Mutat. 2005;25(1):18-21.
Zellner, C., Pullinger, C. R., Aouizerat, B. E., Frost, P. H., Kwok, P. Y., Malloy, M. J., & Kane, J. P. (2005). Variations in human HM74 (GPR109B) and HM74A (GPR109A) niacin receptors. Human Mutation, 25(1), 18-21.
Zellner C, et al. Variations in Human HM74 (GPR109B) and HM74A (GPR109A) Niacin Receptors. Hum Mutat. 2005;25(1):18-21. PubMed PMID: 15580557.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Variations in human HM74 (GPR109B) and HM74A (GPR109A) niacin receptors. AU - Zellner,Christian, AU - Pullinger,Clive R, AU - Aouizerat,Bradley E, AU - Frost,Philip H, AU - Kwok,Pui-Yan, AU - Malloy,Mary J, AU - Kane,John P, PY - 2004/12/8/pubmed PY - 2006/2/28/medline PY - 2004/12/8/entrez SP - 18 EP - 21 JF - Human mutation JO - Hum Mutat VL - 25 IS - 1 N2 - 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. SN - 1098-1004 UR - https://www.unboundmedicine.com/medline/citation/15580557/Variations_in_human_HM74__GPR109B__and_HM74A__GPR109A__niacin_receptors_ L2 - https://doi.org/10.1002/humu.20121 DB - PRIME DP - Unbound Medicine ER -