Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma gene in first-degree relatives of subjects with polycystic ovary syndrome

ergun, mehmet ali/0000-0001-9696-0433WOS: 000234072900004PubMed: 16316841Aim. This study was designed to examine the relationship between the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) gene and insulin resistance (IR) in first-degree relatives of subjects with polycystic ovary syndrome (PCOS). Materials and methods. One hundred and twenty family members of 55 patients with PCOS and 80 unrelated healthy control subjects without a family history of diabetes or PCOS were studied. IR was assessed by homeostatic model assessment (HOMA-IR) and area under the curve (AUC) for insulin during an oral glucose tolerance test in subjects with normal glucose tolerance and controls. Genetic analysis of the PPAR-gamma gene Pro12Ala polymorphism was performed by restriction fragment length polymorphism. Results. Fasting insulin, HONIA-IR and AUC insulin were significantly higher in first-degree relatives of PCOS subjects than in controls. A significantly different allele distribution of the Pro12Ala polymorphism of PPAR-gamma was observed between the two groups, with the frequency of the variant Ala isoform being significantly reduced in the first-degree relatives of PCOS subjects (10.8%, 13 subjects) compared with the control group (22.5%, 18 subjects). All Pro12Ala polymorphisms of the PPAR-gamma gene were heterozygous. Compared with first-degree relatives of PCOS subjects with the Pro12Pro polymorphism of PPAR-gamma, first-degree relatives of PCOS subjects with the Pro12Ala polymorphism had low fasting insulin, HONIA-IR and AUC insulin levels. The combined prevalence rate for impaired glucose tolerance, impaired fasting glucose and diabetes was 40% (16 subjects) in mothers and 52% (20 subjects) in fathers of PCOS women. Conclusion. Our findings suggest that Pro12Ala PPAR-gamma gene polymorphism may be protective against IR and might prevent the development of diabetes mellitus in the first-degree relatives of subjects with PCOS

Calpain 10 gene single-nucleotide 44 polymorphism may have an influence on clinical and metabolic features in patients with polycystic ovary syndrome

ergun, mehmet ali/0000-0001-9696-0433WOS: 000264938300003PubMed: 19337008Aim: This study was designed in order to examine the relationship between Calpain 10 [single-nucleotide polymorphism (SNP) 19,43,44,63] gene polymorphisms and clinical and hormonal characteristics in women with polycystic ovary syndrome (PCOS). Materials and methods: One hundred and seven patients with PCOS and 114 healthy subjects were included in this study. Serum levels of sex steroids were measured for each individual. Insulin resistance (IR) was evaluated by the homeostasis model assessment (HOMA) and quantitative insulin-sensitivity check index (QUICKI) methods. Insulin and glucose responses to the oral glucose tolerance test (OGTT) were analyzed by calculating the areas under the curve for insulin (AUCI) and glucose by the trapezoidal methods. We used PCR and restriction fragment length polymorphism technique to examine Calpain 10 SNP 19, 43, 44, and 63 polymorphisms. Results: Allele distribution of Calpain 10 SNP 44 gene polymorphism was observed as significantly different between the groups. Calpain 10 SNP 44 TC genotype was found to be increased in PCOS subjects (69.15%) compared to the control subjects (50%). However, when compared to control subjects, patients with PCOS had similar Calpain 10 SNP 19, Calpain 10 SNP 43, and SNP 63 gene polymorphisms. When compared with normal Calpain 10 gene SNP 44 allele in PCOS subjects, subjects with PCOS having Calpain 10 gene SNP 44 allele polymorphism had higher free testosterone, androstenedione, DHEA-S, and fasting insulin levels. Also, PCOS women with Calpain 10 gene SNP 44 allele polymorphism had high Ferriman-Gallwey (F-G) score, acne, prevalence of menstrual disturbances, waist-hip ratio, HOMA-IR, AUCI levels and low QUICKI levels. Conclusion: The findings show that Calpain 10 gene SNP 44 allele polymorphism may have a role in PCOS pathogenesis. However, larger-scale studies are needed in this field

Effects of alendronate and pamidronate on apoptosis and cell proliferation in cultured primary human gingival fibroblasts

Dagdeviren, Attila/0000-0001-8990-8282; Senel, Firdevs/0000-0002-4475-0861WOS: 000363214300004PubMed: 25636638Data arising from the recent literature directed the researchers to study on the degree and extent of bisphosphonate toxicity on oral mucosa in further detail. the aim of this study is to determine the half maximal inhibitory concentration of pamidronate (PAM) and alendronate (ALN) on human gingival fibroblasts in vitro using 3-[4.5-thiazol-2-yl]-2.5-diphenyltetrazolium bromide (MTT) assay and to evaluate the effects of both agents on the proliferation and apoptotic indices. Cells used in the study were generated from human gingival specimens and divided into alendronate (n = 240), PAM (n = 240), and control groups (n = 60). Based on the MTT assay results, 10(-4), 10(-5), 10(-6), and 10(-7) M concentrations of both drugs were administered and the effects were evaluated for 6, 12, 24, 48, or 72 h periods. An indirect immunofluorescence technique was used to evaluate apoptotic (anti-caspase 3) and proliferation (anti-Ki67) indices. Toxicity of both PAM and ALN was found to be the most potent at 10(-4)-10(-5) M range. the apoptotic index of PAM group was found to be significantly higher than ALN group for all concentrations especially at 24 h incubation time (p < 0.05). the decrease in the proliferation index was found similar in first 48 h for both drugs; however, after 72 h of incubation decrease in proliferation index in PAM group was found to be significantly higher (p < 0.05). Micromolar concentrations of not only PAM but also ALN rapidly affect cells generated from human oral gingival tissue by inducing apoptosis together with inhibition of proliferation. Cytotoxic effects of both ALN and PAM on primary human gingival fibroblasts, which cause significant changes in apoptotic and proliferative indices as shown in this in vitro study, suggests that the defective epithelialization of oral mucosa is possibly a major factor on the onset of bisphosphonate-related osteonecrosis of the jaw cases.Baskent University Institutional Review BoardBaskent University [D-KA 10/09]; Baskent University Research FundBaskent UniversityThis study was approved by Baskent University Institutional Review Board (Project no: D-KA 10/09) and supported by Baskent University Research Fund