HNF1A gene p.I27L is associated with co-existing preeclampsia in gestational diabetes mellitus.

The association of the FTO gene and HNF1α gene on gestational diabetes mellitus (GDM) and preeclampsia remains unclear. This is the first study to examine whether HNF1α gene and FTO gene were associated with having GDM and preeclampsia in Turkish women. Healthy pregnant women (n = 101) and women with GDM (n = 169) were included. GDM was divided into two groups as GDM-only (n = 90) and GDM-preeclampsia (n = 79). Genotyping of HNF1α gene p.I27L, p.A98V, and p.S487N, and FTO gene rs9939609 SNPs were performed using RT-PCR. The frequency of p.S487N, p.A98V, and FTO genotype were similar between the groups (p > .05). p.I27L GG-wild, GT, and TT genotype were 56.5%, 36.6%, and 6.9% in controls; 40.0%, 51.1%, and 8.9% in GDM-only; and 26.6%, 51.9%, and 21.5% in GDM-preeclampsia (p = .034). TT and GT genotype was more frequent in GDM-preeclampsia than in controls (p < .05). GT genotype was increased in GDM-only compared with controls (p < .05). TT genotype was more frequent in GDM-preeclampsia than in GDM-only (p < .05). p.I27L TT genotype was independently associated with increased blood pressure (BP) and urinary protein. p.I27L TT genotype was associated with increased preeclampsia risk in patients with GDM by increasing BP and urinary protein.

HNF1A gene p.I27L is associated with early-onset, maturity-onset diabetes of the young-like diabetes in Turkey.

BACKGROUND: The molecular basis of the Turkish population with suspected maturity-onset diabetes of the young (MODY) has not been identified. This is the first study to investigate the association between HNF1A-gene single-nucleotide polymorphisms (SNPs) and having early-onset, MODY-like diabetes mellitus in the Turkish population. METHODS: All diabetic patients (N = 565) who presented to our clinic between 2012 and 2015 with a clinical suspicion of MODY were included in the study. Analysis of HNF1A, HNFB, HNF4A, GCK gene mutations was performed using real-time polymerase chain reaction sequencing. After genetic analysis, diabetics (n = 46) with HNF1A, HNF1B, HNF4A, GCK gene mutations (diagnosed as MODY) and diabetics (n = 30) with HNF1B, HNF4A, GCK gene SNPs were excluded. Patients with early-onset, MODY-like diabetes (n = 486) and non-diabetic controls (n = 263) were included. Genetic analyses for the HNF1A gene p.S487 N (rs2464196), p.A98V (rs1800574) and p.I27L (rs1169288) SNPs were performed using Sanger-based DNA sequencing among the control group. RESULTS: p.S487 N and p.A98V was similar between the diabetics and controls in dominant and recessive models with no association (each, p > 0.05). p.I27L GT/TT carriers (GT/TT vs. GG, OR = 1.68, 95% CI: [1. 21-2.13]; p = 0.035) and p.I27L TT carriers had increased risk of having MODY-like diabetes (GT/GG vs. TT, OR = 1.56, 95% CI: [1. 14-2.57]; p = 0.048). Family inheritance of diabetes was significantly more common in patients with the p.I27L TT genotype. The p.I27L SNP was modestly associated with having diabetes after adjusting for body mass index and age (ß = 1.45, 95% CI: [1. 2-4.2]; p = 0.036). CONCLUSIONS: The HNF1A gene p.I27L SNP was modestly associated with having early-onset, MODY-like diabetes in the Turkish population. HNF1A gene p.I27L SNP might contribute to age at diabetes diagnosis and family inheritance.

The VDR gene FokI polymorphism is associated with gestational diabetes mellitus in Turkish women.

BACKGROUND: The association between the vitamin D receptor (VDR) gene and gestational diabetes mellitus (GDM) has not been investigated in Turkish pregnant women. We aimed to investigate associations between VDR gene BsmI (rs15444410), ApaI (rs7975232), FokI (rs19735810), and TaqI (rs731236) single nucleotide polymorphisms (SNPs) and GDM. MATERIAL-METHODS: This case-control study comprised 100 women with GDM and 135 pregnant women without GDM. The VDR polymorphism was evaluated using Sanger-based DNA sequencing. RESULT: VDR gene ApaI, BsmI, and TaqI SNPs did not differ between women with and without GDM (each, p > 0.05). ApaI, BsmI, and TaqI were not associated with GDM risk. The VDR gene FokI CT/TT genotype was associated with an increased GDM risk (CT vs. CC, OR = 1.84, 95% CI: [1.05-3.23], p = 0.031; TT vs. CC, OR = 3.95, 95% CI: [1.56-9.96], p = 0.002; CT/TT vs. CC, OR = 2.29, 95% CI: [1.35-3.89], p = 0.002; and CT/CC vs. TT, OR = 3.02, 95% CI: [1.23-7.38], p = 0.012). The FokI-TT genotype was more associated with younger age and higher glucose, HbA1c, and HOMA-IR than the CC and CT genotype. FokI-T was positively correlated with log-HOMA-IR (r = 0.326, p = 0.004). FokI SNPs were independently associated with GDM after adjusting for BMI and age (ß = 1.63, 95% CI: [1. 2-4.2], p = 0.012). There were no associations between the FokI, ApaI, BsmI and TaqI haplotypes and GDM. CONCLUSION: VDR gene FokI SNPs were independently associated with having GDM in Turkish women. VDR gene FokI SNPs might contribute to insulin resistance of developing GDM.

VDR gene FokI polymorphism as a poor prognostic factor for papillary thyroid cancer.

This is the first study to investigate the effect of vitamin D receptor ( VDR) gene single-nucleotide polymorphisms on the clinicopathologic features of papillary thyroid cancer in Turkey. A total of 165 patients with papillary thyroid cancer and 172 controls were included in this case-control study. VDR gene single-nucleotide polymorphisms FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) were evaluated using reverse-transcription polymerase chain reaction. VDR gene polymorphisms BsmI, ApaI, and TaqI did not differ between the papillary thyroid cancer group and control group (p > 0.05, each). BsmI, ApaI, and TaqI were not associated with papillary thyroid cancer risk. The VDR gene FokI CT/TT genotype was associated with an increased papillary thyroid cancer risk (CT vs CC: odds ratio = 1.71, 95% confidence interval = 1.15-2.76, p = 0.028; TT vs CC: odds ratio = 2.44, 95% confidence interval = 1.29-4.62, p = 0.005; CT/TT vs CC: odds ratio = 1.88, 95% confidence interval = 1.20-2.96, p = 0.006; CT/CC vs TT: odds ratio = 1.80, 95% confidence interval = 1.05-3.20, p = 0.041). VDR gene polymorphisms were not in linkage disequilibrium. The FokI TT genotype was associated with having T3 and T4, stage III/IV, extra-thyroidal invasion. The FokI CT/TT or TT genotype was associated with developing N1 status, multifocality, tumor size ≥10 mm, and treatment with radioiodine therapy. Persistence/recurrence did not differ between the FokI genotypes. Carriers of the FokI T allele were at an increased risk of more advanced tumor-node-metastasis stage, greater tumor size, multifocality, and extra-thyroidal invasion of papillary thyroid cancer compared with the CC genotype. VDR gene FokI T allele and TT genotype correlated with aggressiveness of papillary thyroid cancer; thus, FokI could be useful as a poor prognostic factor to assess the high risk of papillary thyroid cancer.

Protective/restorative Role of the Adipose Tissue-derived Mesenchymal Stem Cells on the Radioiodine-induced Salivary Gland Damage in Rats.

BACKGROUND: To analyze protective/regenerative effects of adipose tissue-derived mesenchymal stem cells (ADMSC) on 131I-Radioiodine (RAI)-induced salivary gland damage in rats. MATERIALS AND METHODS: Study population consisted of controls (n:6) and study groups (n:54): RAI (Group 1), ADMSC (Group 2), amifostine (Group 3), RAI+amifostine (Group 4), concomitant RAI+ADMSC (Group 5) and RAI+ADMSC after 48 h (Group 6). We used light microscopy (LM), transmission electron microscopy (TEM), and salivary gland scintigraphy (SGS), and analyzed data statistically. RESULTS: We observed the homing of ADMSC in salivary glands at 1st month on LM. RAI exposure affected necrosis, periductal fibrosis, periductal sclerosis, vascular sclerosis and the total sum score were in a statistically significant manner (P < 0.05). Intragroup comparisons with LM at 1st and 6th months revealed statistically significant improvements in Group 6 (P < 0.05) but not in Groups 4 and 5. Intergroup comparisons of the total score showed that Groups 4 and 5 in 1st month and Group 6 in 6th month had the lowest values. TEM showed vacuolization, edema, and fibrosis at 1st month, and an improvement in damage in 6th month in Groups 5 and 6. SGSs revealed significant differences for the maximum secretion ratio (Smax) (P = 0.01) and the gland-to-background ratio at a maximum count (G/BGmax) (P = 0. 01) at 1st month, for G/BGmax (P = 0.01), Smax (P = 0.01) and the time to reach the maximum count ratio over the time to reach the minimum count (Tmax/Tmin) (P = 0.03) at 6th month. 1st and 6th month scans showed differences for Smax and G/BGmax (P = 0.04), but not for Tmax/Tmin (p > 0.05). We observed a significant deterioration in gland function in group 1, whereas, mild to moderate deteriorations were seen in protective treatment groups. CONCLUSIONS: Our results indicated that ADMSC might play a promising role as a protective/regenerative agent against RAI-induced salivary gland dysfunction.

Comparison of therapeutic characteristics of islet cell transplantation simultaneous with pancreatic mesenchymal stem cell transplantation in rats with Type 1 diabetes mellitus.

Although, pancreas islet call transplantation is a new, promising method for type 1 diabetic patients, it remains as an experimental procedure applied in selected patients. The present study aimed to investigate effect of pancreatic mesenchymal stem cell transplantation simultaneous with islet cell transplantation on islet liveliness and thus on the treatment of diabetes in type 1 diabetic rats. The study used Wistar Albino Rats and was performed in a total of four groups [control (G1), mesenchymal stem cell (G2), islet (G3) and islet + mesencymal stem cell (G4)] each including 8 rats. Blood glucose level of the rats, in which diabetes model has been created using streptozotocin, was measured after 72 h. Blood samples were obtained from the rats 30 days after transplantation and then, their livers and pancreases were kept in 10% formaldehyde and the experiment was ended. Following staining with H&E, they were morphologically evaluated under a light microscope. Change in mean blood glucose level was statistically significant in G3 and G4 versus G1 and G2 (p = 0.001, p < 0.001, p < 0.001, and p < 0.001 respectively). Histological examination revealed that mean number of islet cells in the pancreases of the rats was higher in G4; difference between the groups was statistically significant (p < 0.001). Transplantation of islet cells together with mesenchymal stem cells showed beneficial effects in terms of prolonging survival of islet grafts suggesting that transplantation of mesenchymal stem cells together with islet cells during clinical islet transplantation may be beneficial in increasing the number of noninsulin-dependent patients in Type 1 diabetes.

Comparison of prednisolone acetate and loteprednol etabonate for the treatment of benzalkonium chloride-induced dry eye syndrome in rats.

PURPOSE: The aim of the current study is to compare the effects of two corticosteroids, prednisolone acetate 1% (PA) and loteprednol etabonate 0.5% (LE), for the treatment of benzalkonium chloride (BAC)-induced dry eye syndrome (DES) in rats. METHODS: DES was established by topical administration of 0.2% BAC, a commonly used preservative in ophthalmic drugs, for 1 week. Rats were divided into 3 groups just after establishment of DES: PA-treated (Group 1, n=10), LE-treated (Group 2, n=10), and vehicle-treated (Group 3, n=10). Rats were treated by topical administration of PA, LE, or vehicle twice daily for 1 week. The Schirmer test, break-up time score, Fluorescein staining, Rose Bengal staining, and inflammatory index scoring (IIS) tests were performed at all weeks. After the end of the study, eyes of the rats were enucleated and analyzed using light microscopy. RESULTS: The mean aqueous tear volume was significantly increased in both PA- and LE-treated rats (P<0.05), although decreased in vehicle-treated rats (P>0.05). Histologically, diffuse inflammatory cell infiltration was observed in vehicle-treated rats, while inflammation induced by BAC was almost completely resolved in both PA- and LE-treated groups. CONCLUSIONS: In the current study, we showed that both PA and LE are effective treatments in a rat model of BAC-induced DES, which is commonly observed in clinics. No significant differences were observed between the 2 corticosteroids in the efficacy of BAC-induced type of DES treatment.

An epileptic case with mosaic ring chromosome 6 and 6q terminal deletion.

Ring chromosomes are rare chromosome disorders that arise usually de novo. Children with ring chromosome 6 have a wide range of intellectual functioning and congenital anomalies. We report an epileptic case of a 10-year-old boy to be mild psychomotor retardation and dysmorphic traits including microcephaly, brachycephaly, flat occiput, large and apparently low set ears, and bilateral syndactyly between his second and third fingers with mosaic ring chromosome 6 and 6q terminal deletion. Peripheral chromosome and fluorescent in situ hybridisation (FISH) analysis of the patient showed mos46,XY,r(6)(p24;q26),del(6)(q27) [30]/46,XY,del(6)(q27) [20] de novo. We presented the patient in the light of literature because the mosaic ring 6 and 6q terminal deletion was different caryotypically from other mosaic ring 6 patients.