Genetic Determinants of Premature Menopause in A Mashhad Population Cohort.

BACKGROUND: Premature menopause is characterized by amenorrhea before age of 40 years, markedly raised serum luteinizing hormone (LH) level, follicle-stimulating hormone (FSH) level and reduced serum level of estradiol. Genome-wide analysis suggested several loci associated with premature menopause. Here, we aimed to analyze association of variants at the MCM8, FNDC4, PRRC2A, TLK1, ZNF346 and TMEM150B gene loci with premature menopause. MATERIALS AND METHODS: In this cross-sectional study, a total of 117 women with premature menopause were compared to 183 healthy women. Anthropometric indices were measured in all participants: height, weight, body mass index (BMI), waist circumference (WC) and wrist circumference. Eight single-nucleotide polymorphisms (SNPs) of the indicated genes (rs16991615, rs244715, rs451417, rs1046089, rs7246479, rs4806660, rs10183486 and rs2303369) were identified from the literature. Genotyping was performed using tetra-ARMS polymerase chain reaction (PCR) and ASO-PCR methods. RESULTS: T allele of the rs16991615, rs1046089, rs7246479 and rs10183486, C allele of rs244715, rs451417 and rs4806660 as well as TT genotype of rs2303369 were associated with an increased risk of premature menopause, likely causing susceptibility to primary ovarian insufficiency (POI) in comparison with C allele. We also found an association between the rs16991615 SNP with premature menopause. Frequency of the minor allele in cases was increased for all SNPs in comparison with controls. All minor alleles, except for rs2303369, showed a statistically significant increased odds ratio (OR). However, after Bonferroni correction for multiple testing, none of the P values were remained significant. CONCLUSION: The selected polymorphisms in MCM8, FNDC4, PRRC2A, TLK1, ZNF346 and TMEM150B genes may potentially affect susceptibility to premature menopause, although replication of the results in larger cohort could clarify this.

Role of aldo-keto reductase family 1 member B1 (AKR1B1) in the cancer process and its therapeutic potential.

The role of aldo-keto reductase family 1 member B1 (AKR1B1) in cancer is not totally clear but growing evidence is suggesting to have a great impact on cancer progression. AKR1B1 could participate in a complicated network of signalling pathways, proteins and miRNAs such as mir-21 mediating mechanisms like inflammatory responses, cell cycle, epithelial to mesenchymal transition, cell survival and apoptosis. AKR1B1 has been shown to be mostly overexpressed in cancer. This overexpression has been associated with inflammatory mediators including nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), cell cycle mediators such as cyclins and cyclin-dependent kinases (CDKs), survival proteins and pathways like mammalian target of rapamycin (mTOR) and protein kinase B (PKB) or AKT, and other regulatory factors in response to reactive oxygen species (ROS) and prostaglandin synthesis. In addition, inhibition of AKR1B1 has been shown to mostly have anti-cancer effects. Several studies have also suggested that AKR1B1 inhibition as an adjuvant therapy could render tumour cells more sensitive to anti-cancer therapy or alleviate the adverse effects of therapy. AKR1B1 could also be considered as a potential cancer diagnostic biomarker since its promoter has shown high levels of methylation. Although pre-clinical investigations on the role of AKR1B1 in cancer and the application of its inhibitors have shown promising results, the lack of clinical studies on AKR1B1 inhibitors has hampered the use of these drugs to treat cancer. Thus, there is a need to conduct more clinical studies on the application of AKR1B1 inhibitors as adjuvant therapy on different cancers.

Isolated dissection of superior mesenteric artery.

Isolated dissection of the superior mesenteric artery is a rare occurrence with a hitherto unknown exact etiology. Patients may present with abdominal symptoms or hemodynamic instability.We herein present a case of spontaneous isolated superior mesenteric artery dissection in a 48-year-old man, who was admitted with epigastric pain. Due to an undiagnosed paced rhythm on the electrocardiogram, he was given fibrinolysis treatment for acute myocardial infarction. On further evaluation, angiography revealed that the cause of pain was the dissection of the superior mesenteric artery. The patient's symptoms were diminished with conservative management, obviating the need for the angioplasty of the superior mesenteric artery.