ABSTRACT
Se ha sugerido que el haplotipo rs3749474T/rs4864548A del gen CLOCK aumentaría el riesgo de obesidad, pero se desconoce el patrón de variabilidad poblacional de estos alelos y del haplotipo. El objetivo de este estudio es determinar el nivel de ligamiento entre los alelos de riesgo rs3749474T y rs4864548A a partir de la base de datos 1000Genomes para confirmar la existencia del haplotipo TA de los polimorfismos rs3749474-rs4864548 del gen CLOCK y su frecuencia cinco macro poblaciones. Se analizó el desequilibrio de ligamiento y las frecuencias haplotípicas para 2504 individuos, de 26 poblaciones, utilizando el estadístico r y la prueba exacta de Fisher. Existe una alta frecuencia del haplotipo TA en Latinoamérica (44,8%), un alto desequilibrio de ligamiento (r= 0,92) a nivel mundial entre esos alelos, una alta diferenciación entre macro poblaciones y una alta homogeneidad al interior de ellas. La evidencia presentada permite sugerir la realización de posteriores estudios de asociación entre este haplotipo y el nivel de riesgo de obesidad y sobrepeso en poblaciones latinoamericanas.
It has been suggested that the rs3749474T/rs4864548A haplotype of the CLOCK gene increases the risk of obesity, but the population variability of these alleles and the haplotype is unknown. This research aims to determine the linkage between the rs3749474T and rs4864548A alleles from the database of 1000Genomes to confirm the existence of the TA haplotype polymorphisms of these alleles and their frequency in five macro populations. Linkage disequilibrium and haplotype frequencies for 2504 individuals from 26 populations were analyzed using the r statistic and Fisher's exact test. There is a high frequency of the TA haplotype in Latin America (44.8%), a high linkage disequilibrium (r2= 0.92) worldwide between these alleles, a high differentiation between macro populations, and a high homogeneity. The evidence warrants further studies on the association between this haplotype and the risk of obesity and overweight in Latin American populations.
ABSTRACT
Biological clock proteins are involved in the regulation of many important physiological processes, including blood pressure. The deletion or mutation of core circadian clock genes may cause elevated blood pressure levels and disrupted blood pressure rhythms, exacerbating vascular function damage, and ultimately leading to the occurrence, development and poor outcome of ischemic stroke. This article reviews the molecular mechanism of biological clock rhythm, the relationship between biological clock gene and blood pressure regulation mechanism, the mechanism of circadian rhythm disorder in the occurrence and development of hypertension, and the relationship between blood pressure rhythm disorder and stroke.
ABSTRACT
Rhythm of blood pressure refers to the circadian variation of blood pressure, which is regulated by clock genes. However, the rhythm disorder of blood pressure increases the risk of stroke. Taking the process of blood pressure regulation as a clue and focusing on the clock gene pathway, this article explores the possible mechanism of period gene regulating renin-angiotensin-aldosterone system in rhythm of blood pressure, so as to provide reference for the in-depth study of the relevant mechanism of rhythm disorder of blood pressure and search for a new target for the primary prevention of cerebrovascular diseases.
ABSTRACT
Objective To study the significance of circadian gene Period2 expression in epithelial ovarian cancer tissues and the effect of gene overexpression on the growth of ovarian cancer xenografts in nude mice. Methods Twenty-two cases of ovarian cancer paraffin specimens in the First Hospital of Shanxi Medical University (ovarian cancer group) were chosed during Jau. 2010 to Dec. 2013, including 8 cases of stageⅠ, 8 cases of stageⅡ, and 6 cases of stageⅢ, while 6 cases of benign ovarian epithelial tumor paraffin specimens were selected as control (benign tumor group). Period2 gene were detected by real-time quantitative PCR and western blot methods in different stages of ovarian cancer tumor tissues. Established theovarian cancer xenografts in nude mice with ovarian cancer cell line SKOV3, and they weredivided into 3 groups (n=8), including the recombinant plasmid group, empty plasmid group and control group. Using gene transfection technique to transfer Period2 gene into tumor tissues, tested the expression of Period2 mRNA in tumor tissues by real-time quantitative PCR after transfection into all nude mice, monitoredthetransplant tumor growth and calculating the tumor inhibition rate,detected the antiapoptotic gene BRE, apoptosis related tumor necrosis factor receptor (TNFR1) andtumor suppressor gene NIX in tumor tissues by real-time PCR and western blot in different groups. Results (1)The expression level of Period2 mRNA in tumor tissues amongovarian cancer group stageⅠ,ⅡandⅢwere respectively 2.59±0.50, 0.47± 0.08 and 0.42 ± 0.08, but benign tumor group was 6.59 ± 1.05. The expression level of Period2 protein in ovarian cancer group stage Ⅰ,Ⅱ and Ⅲ were respectively 0.835 ± 0.087, 0.412 ± 0.035 and 0.199 ± 0.031, while benign tumor group was 0.874 ± 0.094. The expression level of Period2 mRNA and protein in benign tumor group was higher than those in ovarian cancer group stageⅠ,ⅡorⅢ(P<0.01). With ovarian cancer stage increased, the expression of Period2 mRNA and protein were decreased or absent (P<0.05).(2)Two weeks after transfection, the expression level of Period2 mRNA in recombinant plasmid group tumor tissue was significantly higher than those in the empty plasmid group or the control group (6.11±0.56 vs 0.50±0.09 vs 0.44 ± 0.08, respectively;P<0.01), the transplanted tumor volume of recombinant plasmid group was significantly less than those in empty plasmid group or the control group[ (486±70) mm3 vs (835±106) mm3 vs (846 ± 110) mm3, respectively;P<0.01], the tumor inhibition rate of the recombinantin plasmid group was as high as 42.9%, that was significantly higher than those in the empty plasmid group and the control group (3.8% and 0, respectively;P<0.05).(3)The expression level of BRE mRNA and protein in transplanted tumor tissues in the recombinant plasmid group were significantly lower than those in empty plasmid group and the control group;the expression level of TNFR1 and NIX were significantly higher than those in the empty plasmid group and the control group (all P<0.05). Conclusions Period2 mRNA and protein expression are absent in ovarian cancer of advanced stage. Transfection and stable expression of Period2 gene could slow down the growth of ovarian cancer, and the tumor inhibition rate could be significantly increased. Period2 gene may promote ovarian cancer cells apoptosis through inhibition of BRE gene expression and promoting TNFR1, NIX gene expressionto exert anti-tumor effect.