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

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.     

Nicotinic acid/niacinamide and the skin

Nicotinic acid (also generally known as niacin) and niacinamide (also known as nicotinamide) are similarly effective as a vitamin because they can be converted into each other within the organism. The blanket term vitamin B(3) is used for both. Niacinamide is a component of important coenzymes involved in hydrogen transfer. Here, the two codehydrogenases, nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) are of central importance. Topical application of niacinamide has a stabilizing effect on epidermal barrier function, seen as a reduction in transepidermal water loss and an improvement in the moisture content of the horny layer. Niacinamide leads to an increase in protein synthesis (e.g. keratin), has a stimulating effect on ceramide synthesis, speeds up the differentiation of keratinocytes, and raises intracellular NADP levels. In ageing skin, topical application of niacinamide improves the surface structure, smoothes out wrinkles and inhibits photocarcinogenesis. It is possible to demonstrate anti-inflammatory effects in acne, rosacea and nitrogen mustard-induced irritation. Because of its verifiable beneficial effects, niacinamide would be a suitable component in cosmetic products for use in disorders of epidermal barrier function, for ageing skin, for improving pigmentary disorders and for use on skin prone to acne.     

Bound niacin in sorghum and its availability

Two varieties of Sorghum vulgare, milo and jowar, have been studied. Samples cooked at neutral pH gave total niacin values of 46 and 29 mg/kg, respectively, on an air-dry basis. In extracts made from these at neutral pH and fractionated after gel-filtration, most of the niacin was in high molecular weight (i.e., bound) forms. In a bioassay for niacin, the boiled milo gave a growth response equivalent to 34% of its total niacin being available to young rats. Sorghum has behaved similarly to other mature cereal grains in these tests of niacin availability.     

Dietary supplements in dermatology: A review of the evidence for zinc,biotin, vitamin D,nicotinamide, and Polypodium

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