Asociación entre el polimorfismo c.1-765G>C del gen de la COX-2 y el deterioro cognitivo en individuos diabéticos de 65 o mas años de un Servicio de Geriatría en Monterrey, México / Association between polymorphism c.1-765G>C of the COX2 gene and cognitive impairment in individuals 65 years or more with diabetes from a Geriatric Service in Monterrey, Mexico

Background and objective: Cognitive impairment and dementia are common geriatric syndromes in diabetic patients. Inflammation plays a crucial role in the pathophysiology of Alzheimer's disease and cognitive impairment. Cyclooxygenases (COX) 1 and 2 participate in inflammation. The polymorphism c.1-765G>C of the COX2 gene might be protective against cognitive decline in Mexicans with diabetes mellitus through its reduced promotor activity. To determine the association between polymorphism c.1-765G>C of the COX2 gene and cognitive impairment in elderly adults with diabetes. Patients and methods: Case-control study. We included diabetic patients from the Geriatric Clinic of General Hospital No. 17 who were over 65 years and accepted to participate. Cases were patients with a score of 24 or less on the Mini Mental Status Examination (MMSE) and with DSM IV criteria for dementia. Controls were those with MMSE scores of 25 or greater. Results: We included 97 patients (50 cases and 47 controls). There were no differences regarding clinical and laboratory characteristics between cases and controls. The frequency of the C allele and the CG genotype was higher in controls than in cases and this difference remained significant in a multivariate analysis with an odds ratio of 0.012 (95% CI 0.001-0.091) and 0.009 (95% CI 0.001-0.076) in the bivariate and multivariate analysis, respectively, using the GG genotype frequency as a reference. Conclusion: Cognitive impairment in Mexican patients with diabetes is associated with less exposure to the CG genotype of the c.1-765G>C polymorphism of COX2 (AU)

Fundamento y objetivo: El deterioro cognitivo y la demencia son síndromes geriátricos frecuentes en los pacientes con diabetes. La inflamación es crucial en la fisiopatología de la enfermedad de Alzheimer y del deterioro cognitivo. Las ciclooxigenasas (COX) 1 y 2 participan en la inflamación. El polimorfismo c.1- 765G>C de la COX-2 protegería contra el deterioro cognitivo en adultos mayores diabéticos mexicanos por su menor actividad promotora. El objetivo de este estudio fue determinar la asociación entre el polimorfismo c.1-765G>C del gen de la COX-2 y el deterioro cognitivo en adultos mayores diabéticos. Pacientes y métodos: Estudio de tipo casos y controles. Se incluyeron pacientes diabéticos de la clínica de Geriatría del Hospital General de Zona No. 17, mayores de 65 años que aceptaron participar. Los casos fueron los pacientes con puntuación de 24 o menor en el Mini-Mental State Examination (MMSE) y criterios DSM-IV para demencia. Los controles tenían una puntuación de 25 o mayor en el MMSE. Resultados: Se incluyeron 97 pacientes (50 casos y 47 controles). No hubo diferencias respecto a las características clínicas y de laboratorio entre los casos y los controles. La frecuencia del alelo C y del genotipo CG fue mayor en los controles que en los casos, y dicha diferencia permaneció significativa en el análisis multivariado, con una razón de momios de 0,012 (IC 95% 0,001 a 0,091) y de 0,009 (IC 95% 0,001 a 0,076), en el análisis bivariado y multivariado, respectivamente, tomando como referencia la frecuencia genotípica GG. Conclusión: El deterioro cognitivo en pacientes mexicanos con diabetes se asocia con una menor exposición al polimorfismo c.1-765G>C del gen de la COX-2 (AU)

ESR1 and PGR gene promoter methylation and correlations with estrogen and progesterone receptors in ductal and lobular breast cancer.

The aim of this work was to analyze methylation of the promoter sites of the ESR1 and PGR genes and to determine correlations with immunohistochemical expression of estrogen and progesterone receptors in ductal and lobular breast cancers. An observational, descriptive, molecular study was conducted on 20 ductal and 20 lobular breast cancer samples with immunohistochemical determination of estrogen and progesterone receptor expression. The methylation analysis of ESR1 and PGR promoter sites was carried-out by methylation-specific PCR. For correlation analysis, Kendall's tau coefficient was determined. Positive correlations were found between estrogen and progesterone receptors, estrogen receptor and unmethylated progesterone receptor, progesterone receptor, and unmethylated progesterone receptor. Negative correlations were found between estrogen receptor and methylated progesterone receptor, progesterone receptor and methylated progesterone receptor, methylated and unmethylated estrogen receptor, and methylated and unmethylated progesterone receptor. The results suggest that methylation of promoter sites of ESR1 and PGR is a relatively uncommon event in ductal and lobular breast cancer, and also suggest that the determination of epigenetic states of ESR1 and PGR could represent an alternative or complement to the histopathological expression analysis.

CTCF and CTCFL mRNA expression in 17ß-estradiol-treated MCF7 cells.

Estrogens play a key role in breast cancer, with 60-70% of the cases expressing estrogen receptors (ERs), which are encoded by the ESR1 gene. CTCFL, a paralogue of the chromatin organizer CTCF, is a potential biomarker of breast cancer, but its expression in this disease is currently controversial. A positive correlation has been reported between CTCFL and ERs in breast tumors and there also exists a coordinated interaction between CTCF and ERs in breast cancer cells. Therefore, there appears to be an association between CTCF, CTCFL and estrogens in breast cancer; however, there has been no report on the effects of estrogens on CTCF and CTCFL expression. The aim of this study was to determine the effect of 17ß-estradiol (E2) on the CTCF and CTCFL mRNA expression in the MCF7 breast cancer cell line. The promoter methylation status of CTCFL and data mining for estrogen response elements in promoters of the CTCF and CTCFL genes were also determined. The transcription of CTCF and CTCFL was performed by quantitative polymerase chain reaction (qPCR) and the promoter methylation status of CTCFL was determined by methylation-specific PCR. The MCF7 cells exhibited basal transcription of CTCF, which was significantly downregulated to 0.68 by 1 µM E2; basal or E2-regulated transcription of CTCFL was not detected. Under basal conditions, the CTCFL promoter was methylated. Through data mining, an estrogen response element was identified in the CTCF promoter, but no such element was found in CTCFL. These results suggested that estrogens may modulate CTCF expression, although there was no apparent association between ERs and CTCFL.

Association between polymorphism c.1-765G>C of the COX2 gene and cognitive impairment in individuals 65 years or more with diabetes from a Geriatric Service in Monterrey, Mexico.

BACKGROUND AND OBJECTIVE: Cognitive impairment and dementia are common geriatric syndromes in diabetic patients. Inflammation plays a crucial role in the pathophysiology of Alzheimer's disease and cognitive impairment. Cyclooxygenases (COX) 1 and 2 participate in inflammation. The polymorphism c.1-765G>C of the COX2 gene might be protective against cognitive decline in Mexicans with diabetes mellitus through its reduced promotor activity. To determine the association between polymorphism c.1-765G>C of the COX2 gene and cognitive impairment in elderly adults with diabetes. PATIENTS AND METHODS: Case-control study. We included diabetic patients from the Geriatric Clinic of General Hospital No. 17 who were over 65 years and accepted to participate. Cases were patients with a score of 24 or less on the Mini Mental Status Examination (MMSE) and with DSM IV criteria for dementia. Controls were those with MMSE scores of 25 or greater. Results We included 97 patients (50 cases and 47 controls). There were no differences regarding clinical and laboratory characteristics between cases and controls. The frequency of the C allele and the CG genotype was higher in controls than in cases and this difference remained significant in a multivariate analysis with an odds ratio of 0.012 (95% CI 0.001-0.091) and 0.009 (95% CI 0.001-0.076) in the bivariate and multivariate analysis, respectively, using the GG genotype frequency as a reference. CONCLUSION: Cognitive impairment in Mexican patients with diabetes is associated with less exposure to the CG genotype of the c.1-765G>C polymorphism of COX2.