CMC1R and Multiple Sclerosis

MC1R RHC variants R151C, R160W, and D294H have been associated with increased risk of multiple sclerosis (MS),407,408 while the D84E allele was associated with increased severity of MS.407 This association was unexpected, as increased UVexposure or vitamin D synthesis is associated with a decreased risk of MS. The hypothesized explanations for this discrepancy include that RHC variant allele carriers behave in a sun avoidant manner, or that the loss of MC1R-mediated anti-inflammatory effects...

MC1R Variant Allele Function

Although the genetic association of certain MC1R variant alleles with red hair color and skin cancer risk has been established, the molecular basis underlying these associations must be investigated to give a more complete understanding. The in vitro functional ability of some of these variants has largely been investigated in heterologous overexpression systems with varying results. The major R variants such as R151C were originally thought to be null mutations.251 Since then, many of the RHC...

B Ghrhr Polymorphisms

Polymorphisms in the GHRHR have been reported but no role in IGHD disease has been established.78,127 On the other hand, some polymorphisms (A57T and M422T) have been associated with an increased response to GHRH through an augmented cAMP production.138,139 Although the presence of constitutively active GHRHR mutations could in theory be considered crucial for the development of GH-secreting pituitary tumors, several studies reported no increased risks of developing acromegaly in patients...

DMC1R and Vitiligo

Vitiligo is a pigmentary disorder resulting in pale patches on the skin due to the loss of melanocytes. Interestingly, one study has found a higher frequency of the R160W MC1R allele in controls than in vitiligo patients,409 leading the authors to suggest that the R160W allele is protective against vitiligo. The suggested explanation for this protective function is due to the R160W substitution resulting in an epitope with lower antigenicity, thus protecting the carrier melanocytes against the...

A Ghrhr and Its Ligand

GHRH is synthesized in the hypothalamus as a 107 108 amino acid precursor (prepro-GHRH) (the 108 isoform contain an extra serine in the carboxy-terminal region), which is later processed to give two peptides GHRH(1-44)-NH2 and GHRH(1-40)-0H with similar functions and potency in stimulating GH release.21 Only the first 29 residues are required to exhibit full biological activity.22 GHRH has a plasma half-life of 7-50 min23-25 and it is degraded to inactive forms by dipeptidyl-peptidase type IV...

Melanogenic Enzymes and Pigmentation Genes

Seiji and coworkers50 showed that the TYR enzyme was primarily found in melanin-filled melanosomes, indicative of the role of TYR in melanin production. TYR was cloned in 1987 and found to map to the mouse albino c-locus.51 Loss of function mutations in the human TYR gene are known to cause the disease oculocutaneous albinism type 1 (OCA1).52 This results in hypopig-mentation of the skin, hair, and eyes due to the inability to synthesize melanin. SNPs within the TYR locus have been associated...

A Ghrhr Mutations

The first naturally occurring GHRHR gene mutation was reported in rodents. Dwarf mice were found at the Jackson Laboratories in the 1970s. The dwarf phenotype, inherited as an autosomal recessive character, was later associated with isolated lack of GH.107 Because of its size, the mouse was named little (lit lit), and it soon became a popular model for IGHD studies. GHRH was found to be ineffective in the little mouse108,109 and, after the cloning and characterization of the GHRHR gene,66,67...

The Role of GPR54 in Central Precocious Puberty

Precocious puberty is defined as the development of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys, and can be divided in two major groups according to the etiology gonadotropin-dependent precocious puberty, also known as central or true precocious puberty and gonadotropin-independent precocious puberty, also called peripheral precocious puberty.81 Central precocious puberty (CPP) results from premature activation of hypothalamic GnRH secreting neurons...

KISS1GPR54 and Cancer

Northern blot analyses comparing mRNAs from a panel of human melanoma cells revealed that KISS1 mRNA expression occurred only in nonmetastatic melanoma cells.19 Transfection of a full-length KISS1 cDNA into highly metastatic human melanoma cell lines (C8161) suppressed metastasis to the lung by more than 95 following intravenous or orthotopic injection in an expression-dependent manner, suggesting that KISS1 expression was capable to suppress the metastatic potential of malignant melanoma...