Association between polymorphisms of the androgen and vitamin D receptor genes with prostate cancer risk in a Mexican population / Asociación entre polimorfismo de andrógenos y receptores de vitamina D con riesgo de cáncer prostático en una población mexicana

Introduction. Prostate cancer (PCa) is a worldwide health issue, because of its high incidence and mortality. Its etiology is complex and includes certain risk factors such as age, hormonal status, ethnic origin and family history of PCa. Genetic predisposition is proposed as a major risk factor and there are several controversial reports on the association of PCa and gene polymorphism such as the receptors of the androgen receptor (AR) and the vitamin D (VDR). Objective. To evaluate the CAG triplets repetitions in the first exon of the AR and polymorphisms in the restriction site Taql in the VDR in Mexicans with PCa. Material and methods. A total of 68 Mexicans with histopathological diagnosis of PCa and 48 healthy Mexican with normal prostate specific antigen and rectal exam where included. 10ml of peripheral blood were extracted to isolate DNA and the polymorphisms were evaluated with specific primers for the AR and VDR. Results. The allelic and genetic distributions of the AR and VDR polymorphisms were consistent with the Hardy-Weinberg equilibrium, and there were no statistical differences between the PCa patients and controls (p > 0.05). However, there was a statistical difference between the number of CAG repeats in younger patients with PCa compared to controls (p = 0.045) but when the young patient group was compared versus the elder group there was not stadistically difference (p = 0.085), but the results showed a tendency towards less repetitions of CAG in elder patients. Concerning the VDR, when we analyzed the patients with PCa and a bad pathological prognosis they had a less frequent genotype of TT (p = 0.03). Conclusions. Our results suggest an association between the VDR and AR gene polymorphisms, and the hystopathological score and age at diagnosis in Mexican patients with PCa, respectively. However, it is important to confirm these results in a larger scale study.

Introducción. El cáncer de próstata (PCa) es un problema de salud mundial, tanto por su elevada incidencia como mortalidad. Su etiología es compleja e incluye factores de riesgo reconocidos como la edad, estado hormonal, origen étnico y antecedentes familiares de PCa. El fondo genético es un factor de riesgo y existen reportes controversiales de la asociación de PCa y polimorfismos en los genes como son los receptores de vitamina D (VDR) y el de andrógenos (AR). Objetivo. Evaluar las repeticiones de tripletes de CAG en el primer exon del AR y polimorfismos en el sitio de restricción Taql en el VDR en mexicanos con PCa. Material y métodos. Se incluyeron 68 mexicanos con diagnóstico histopatológico de PCa y 48 mexicanos con niveles normales de antígeno prostático y tacto rectal normal. Se les extrajo 10 mL de sangre periférica para aislar DNA y mediante olígos específicos se evaluaron los polimorfismos mencionados. Resultados. La distribución alélica y genotípica de los polimorfismos en el AR y VDR fueron consistentes con el equilibrio de Hardy-Weinberg, y no mostraron diferencias significativas entre los casos y controles (p > 0.05). Sin embargo, el número de repeticiones de CAG en el AR fueron estadísticamente diferentes en pacientes jóvenes con PCa comparados con los controles (p = 0.045), cuando se comparó el grupo de pacientes de jóvenes contra aquellos mayores de 60 años no se encontró diferencia estadísticamente significativa (p - 0.085); sin embargo, se observó una tendencia de un número menor de repetidos CAG en pacientes mayores con PCa. Por otra parte, al comparar VDR en los pacientes con PCa de mal pronóstico por el patrón histológico tenían menor frecuencia de genotipos TT (p - 0.03). Conclusiones. Nuestros resultados sugieren una asociación entre los polimorfismos de los genes del VDR y AR, y el patrón histológico y la edad al diagnóstico en pacientes mexicanos con PCa, respectivamente. Sin embargo, es necesario confirmar estos resultados en un estudio con mayor número de pacientes.

Linkage disequilibrium between IDUA kpnI-VNTR Haplotype in mexican patients with MPS-I

Background. The MPS-I is an autosomal recessive disorder caused by mutations in the IDUA gene that induce to a deficiency of glycosidase Ó-L-iduronidase that is required for degradation of heparan and dermatan sulfate. This disorder expresses a wide range of clinical symptoms. Methods. Kpnl (k) and VNTR (V) intragenic polymorphisms at the IDUA gene were studied in mestizo and Huichol Indian Mexican populations as well in 13 MPS-I patients. Data from Australian normal and MPS-I (2-4) individuals were also studied. Results. Genotypes for IDUA K and V sites in Mexicans were in agreement with hardy-Weinberg expectations, except for stie K in Huichols, Individually, allele frequency distributions were different (p< 0.05) in the two normal groups for the V site. K-V haplotype frequency distributions (HFDs) in these two normal groups were also different as compared with normal Australians. In Mexican MPS-I patients, HFD was different (p <0.05) with or MPS-I Australians. This can be taken as evidence of linkage disequilibrium between K-V polymorphism and MPS-I gene mutation(s) at the IDUA region. A similar finding was reported. However, disequilibrium in Mexicans was determined by haplotypes different from those in Australia. In Mexican MPS-I patients, haplotype K2-V1 is increased and K1-V3 decreades with respect to the Mexican mestizo (p < 0.05), while in Australians, MPS-I patients had an increase of haplotypes K2-V2 and K1-V2 with respect to expected frequency. Conclusions. The similar HFD between Mexican and australian MPS-I patients suggests a common genetic origin, that MPS-I mutations were introduced to Mexico by Spaniards, and that such mutations predate the dispersion between Mexican and Australian Caucasian ancestors. The differences in disequilibrium are explained rather by genetic drift