Thyroid hormones have crucial developmental effect during fetal life. This study investigates the effects of maternal hypothyroidism on the carbohydrate metabolism and insulin secretion capacity of islets of the adult male offspring of rats. One group of pregnant mothers (fetal hypothyroid) of Wistar rats drank water containing 0.02% of 6-propyl-2-thiouracil during pregnancy, while the control group consumed only tap water. After delivery, survival and weight of the neonates from both groups were followed. In adult male offspring, the intravenous glucose tolerance test was performed and 5-6 weeks later, glucose-stimulated insulin secretion of isolated islets was assessed. Plasma glucose concentration of the fetal hypothyroid group during intravenous glucose tolerance test was significantly higher (p=0.003) at 5-20 min as compared to the control group, whereas plasma insulin concentration was significantly lower (p=0.012) at 5-20 min. Insulin secretion of the isolated islets stimulated with 16 mM glucose of the offspring in the fetal hypothyroid group (376.2 ± 57.1 pmol/islet/60 min) was significantly lower (p=0.02) as compared to the control group (618.1 ± 85.2). Although adult offspring born from hypothyroid mothers were euthyroid, their glucose tolerance and glucose stimulated insulin secretion of islets were altered, which may eventually contribute to the development of diabetes.

SIRT2 is a member of sirtuin family and is associated with cell growth in various cancers. In this study, we searched for variants in functional region of SIRT2 gene and identify rs2015 and rs2241703 in the 3′UTR with minor allele frequency >0.05 in Chinese Han Beijing population from 1000 Genomes Project. We then genotyped these two variants in 842 colorectal cancer (CRC) patients and 1,718 healthy controls using Taqman genotyping assay. Association between variants and risk of CRC is calculated using logistic regression adjusted for sex and age. We found that rs2015C was significantly associated with increased risk of CRC. Compared with CC genotype carriers, CA genotype and AA genotype carriers were associated with CRC susceptibility with OR being 0.79 (95% CI: 0.65-0.96, P = 0.019) and 0.73 (95% CI: 0.58-0.92, P = 0.009), respectively. When stratified by sex and age, significant associations were observed only in males (OR = 0.82, 95% CI: 0.71-0.96, P = 0.010) for rs2015, but not females (OR = 0.90, 95% CI: 0.73-1.10, P = 0.287). It is suggested that the sequence including rs2015C allele lies within a binding site for the full seed region of hsa-miR-376a-5p. Through a systematic interrogate of variants in the functional region of SIRT2 gene, we identified rs2015 was significantly associated with CRC susceptibility, providing new insights into the carcinogenesis of CRC.

Background: Vitamin D and insulin play an important role in susceptibility to polycystic ovary syndrome (PCOS), and therefore vitamin D receptor (VDR), parathyroid hormone (PTH), and insulin receptor (INSR) gene variants might be involved in the pathogenesis of PCOS. Objective: The present study was designed to investigate the possible associations between polymorphisms in VDR, PTH, and INSR genes and the risk of PCOS. Materials and Methods: VDR, PTH, and INSR gene variants were genotyped in 35 women with PCOS and 35 controls using Polymerase chain reaction -Restriction fragment length polymorphism method. Furthermore, serum levels of glucose and insulin were measured in all participants. Results: No significant differences were observed for the VDR FokI, VDR Tru9I, VDR TaqI, PTH DraII, INSR NsiI, and INSR PmlI gene polymorphisms between the women with PCOS and controls. However, after adjustment for confounding factors, the VDR BsmI "Bb" genotype and the VDR ApaI "Aa" genotype were significantly under transmitted to the patients (p= 0.016; OR= 0.250; 95% CI= 0.081-0.769, and p= 0.017; OR= 0.260; 95% CI= 0.086-0.788, respectively). Furthermore, in the women with PCOS, insulin levels were lower in the participants with the INSR NsiI "NN" genotype compared with those with the "Nn + nn" genotypes (P= 0.045). Conclusion:The results showed an association between the VDR gene BsmI and ApaI polymorphisms and PCOS risk. These data also indicated that the INSR "NN" genotype was a marker of decreased insulin in women with PCOS. Our findings, however, do not lend support to the hypothesis that PTH gene DraII variant plays a role in susceptibility to PCOS.

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Background: Substantial evidence from epidemiological studies has suggested that increased levels of calcium may play a protective role against colorectal cancer (CRC). Given the vital role of calcium sensing receptor (CaSR) and parathyroid hormone (PTH) in the maintenance of calcium homeostasis, we explored whether the rs1801725 (A986S) variant located in exon 7 of the CaSR gene and the rs6256 variant located in exon 3 of PTH gene might be associated with CRC risk. Materials and Methods: In this study 860 subjects including 350 cases with CRC and 510 controls were enrolled and genotyped using PCR-RFLP methods. Results: We observed no significant difference in genotype or allele frequencies between the cases with CRC and controls for both CaSR and PTH genes either before or after adjustment for confounding factors including age, BMI, sex, smoking status, and family history of CRC. Furthermore, no evidence for effect modification of any association of rs1801725 and rs6256 variants and CRC by BMI, sex, or tumor site was observed. In addition, there was no significant difference in genotype and allele frequencies between the normal weight (BMI <25 kg/m 2 ) cases and overweight/ obese (BMI ≥25 kg/m 2 ) cases for the two SNPs. Conclusions: These data indicated that the CaSR gene A986S variant is not a genetic contributor to CRC risk in the Iranian population. Furthermore, our results suggest for the first time that PTH gene variant does not affect CRC risk. Nonetheless, further studies with larger sample size are needed to validate these findings.