A case-control study of MC1R variants in Greek patients with basal cell carcinoma: increased risk independently of pigmentary characteristics.

Melanocortin 1 receptor (MC1R) gene variants are a major contributor to pigmentation characteristics and the modulation of sporadic basal cell carcinoma (BCC) risk. This is a hospital-based, case-control study to investigate the association of MC1R variants and pigmentary characteristics with the risk of BCC development in a Southern European population in Greece. In total, 141 patients with BCC and 166 controls were studied. Increased BCC risk was found for the presence of 2 or more MC1R variants (OR:3.07, 95% CI:1.13-8.34), or 2 or more variants of which at least 1 was major function (OR:7.15, 95% CI:1.37-5.52), after adjustment for the 'red hair colour' (RHC) phenotype. Increased BCC risk persisted in the presence of 2 or more MC1R variants (OR:4.15, 95% CI:1.35-12.72), after adjustment for potential confounding factors including skin color (P:0.237) and atypical nevi (OR:9.57, 95% CI:2.19-41.81, P:0.003). MC1R genotype is a risk factor for the development of BCC in Greek patients independently of pigmentary characteristics, and the combination of MC1R variants may modulate this risk.

A study of a single variant allele (rs1426654) of the pigmentation-related gene SLC24A5 in Greek subjects.

The SLC24A5 gene, the human orthologue of the zebrafish golden gene, has been shown to play a key role in human pigmentation. In this study, we investigate the prevalence of the variant allele rs1426654 in a selected sample of Greek subjects. Allele-specific polymerase chain reaction was performed in peripheral blood samples from 158 attendants of a dermatology outpatient service. The results were correlated with pigmentary traits and MC1R genotype. The vast majority of subjects (99%) were homozygous for the Thr(111) allele. Only two subjects from the control group (1.26%) were heterozygous for the alanine and threonine allele. Both of these Thr(111)/Ala(111) heterozygotes carried a single polymorphism of MC1R (one with the V92M variant and another with the V60L variant). Following reports of the rs1426654 polymorphism reaching fixation in the European population, our study of Greek subjects showed a prevalence of the Thr(111) allele, even among subjects with darker skin pigmentation or phototype.

Observation of a rare hemoglobin variant [Hb Lulu island, beta107(G9)Gly-->Asp, GGC-->GAC] co-inherited with a beta+-thalassemia mutation [IVS-I-110 (G-->A)] or in the heterozygous state in a Greek-Albanian family.

We report clinical, hematological, biochemical, functional and molecular studies carried out on two first cousins from a Greek-Albanian family who have clinical and hematological findings consistent with the diagnosis of thalassemia intermedia. DNA studies determined that they had co-inherited a common Mediterranean beta-thalassemia (thal) mutation, IVS-I-110 (G-->A), in trans to a beta-globin gene mutation at codon 107 (GGC-->GAC), predicted to give rise to a rare unstable beta chain variant Hb Lulu Island or beta107(G9)Gly-->Asp.

Melanocortin receptor-1 gene polymorphisms and the risk of cutaneous melanoma in a low-risk southern European population.

Individuals with melanocortin 1 receptor (MC1R) gene variants have been shown to carry an increased risk for the development of melanoma. In this study, we investigated the relationship of MC1R gene variants and the risk of melanoma in 123 melanoma patients and 155 control subjects from Greece. The entire MC1R gene was sequenced for polymorphisms and the results were correlated with host factors and pigmentary characteristics. MC1R polymorphisms were present in 59.4% of melanoma patients compared to 37.5% of controls, yielding an odds ratio (OR) of 2.43 (95% confidence interval (CI) = 1.50-3.96, P < 0.001) for melanoma among MC1R carriers. The risk of melanoma was enhanced in individuals carrying multiple variant alleles (OR = 6.97; 95% CI = 1.86-26.12, P = 0.004). Only the Val60Leu, Arg142His, and Arg151Cys variants were significantly associated with melanoma risk. In stratified analysis, the risk of melanoma among MC1R carriers was not influenced by skin phototype, skin color, or hair color. No association was found between MC1R genotype and the age of onset of melanoma, the tumor location, or the tumor thickness. In conclusion, MC1R polymorphisms are a predisposing factor of melanoma in a southern European population with a relatively low incidence of the disease.

A rare 33 bp in-frame deletion (alpha63-74 or alpha64-74 or alpha65-75) in the alpha1-globin gene causing alpha(+)-thalassemia: a second observation.

The most frequent defects resulting in alpha-thalassemia (thal) include large deletions that remove one or both of the duplicated alpha-globin genes on chromosome 16. Less commonly, alpha-thal mutations involve single nucleotide substitutions or micro-deletions, leading either directly to decreased alpha-globin chain synthesis by the affected allele, or indirectly through production of hyperunstable variant alpha-globin chains. Here we describe the characterization of a 33 bp in-frame deletion within the alpha1-globin gene, in a woman with hematological findings consistent with an alpha-thal trait. The amino acids predicted to be missing as a result of the 33 bp deletion are at the end of the E helix and the EF corner of the alpha-globin protein chain, and are not normally involved in the heme contact, although it is presumed that alpha-globin chain folding and hemoglobin (Hb) formation will be disrupted. The observation of inclusion and Heinz bodies indicates the synthesis of some abnormal Hb (or globin chains). An identical mutation has been previously observed in a single case, a Canadian individual of Greek descent, indicating that it is a rare mutation, and probably of the same origin. Possible mechanisms underlying the mutation at the DNA level are discussed.