Spectrum of Genetic Mutation in Beta Globin Gene in Various Type of Thalassaemia in Bangladesh

Background: Hb-E/Beta thalassaemia is a congenital haemoglobin disorder which is a compound heterozygous state consists of qualitative disorder like Hb E variant & quantitative Hb disorder caused by genetic mutation of Beta chain. Objective: The aim of the study was to identify the beta gene mutation in Hb E/Beta thalassaemia. Method: A total of 32 diagnosed Hb E/Beta thalassaemia patients were included in this cross-sectional study from May 2019 to July 2020. Genetic analysis was done by sanger sequencing. Results: In this observational study, we found 13 different types of Beta gene mutations. Heterozygous for IVS 1-5(G>C) mutation was most frequent (53.1%). Conclusion: Genetic mutation is the confirmatory diagnosis for thalassaemia as well as one of the main factors for clinical expression. Mutation pattern also varies according to the geographical distribution. So, this study shows the frequently found mutation in Bangladesh and should carry out routinely to point out phenotypic expression.

Increased Plasma FGF21 and Activated FGF21 Signaling in Adipose Tissue and Its Possible Association With Insulin Sensitivity in Specific GDM Subtype

Background: To study the discrepancy of the insulin sensitivity alteration pattern, circulating fibroblast growth factor (FGF21) levels and FGF21 signaling in visceral white adipose tissue (vWAT) of gestational diabetes mellitus (GDM) subtypes.Methods: 26 GDM women with either a predominant of insulin-secretion defect (GDM-dysfunction, n = 9) or insulin-sensitivity defect (GDM-resistance, n = 17)] and 13 normal glucose tolerance (NGT) women scheduled for caesarean-section at term were studied. Plasma and vWAT samples were collected at delivery.Results: The insulin sensitivity was improved from the 2nd trimester to delivery in the GDM-resistance group. Elevated circulating FGF21 concentration at delivery, increased FGF receptor 1c and decreased klotho beta gene expressions, enhanced ERK1/2 phosphorylation, and increased GLUT1, IR-B, PPAR-γ gene expressions in vWAT were found in the GDM-resistance group as compared with the NGT group. The circulating FGF21 concentration was negatively correlated with fasting blood glucose (r = -0.574, P < 0.001), and associated with the GDM-resistance group (r = 0.574, P < 0.001) in pregnant women at delivery. However, we observed no insulin sensitivity alteration in GDM-dysfunction and NGT groups during pregnancy. No differences of plasma FGF21 level and FGF21 signaling in vWAT at delivery were found between women in the GDM-dysfunction and the NGT group. Conclusions: Women with GDM heterogeneity exhibited different insulin sensitivity alteration patterns. The improvement of insulin sensitivity may relate to the elevated circulating FGF21 concentration and activated FGF21 signaling in vWAT at delivery in the GDM-resistance group.Trial registration: ChiCTR, ChiCTR 1900026735, registered 20 October 2019, https://www.chictr.org.cn/25/showproj.aspx?proj=44559

Status of Estrogen Receptor Beta Gene Polymorphisms rs1256049 and rs4986938 in a cohort of South Indian women with Primary ovarian insufficiency

The current study is aimed to investigate the role of estrogen receptor beta gene polymorphisms for causation of Primary Ovarian insufficiency (POI) in south Indian women. Primary Ovarian insufficiency (POI) is a menstrual disorder presenting with Primary and secondary amenorrhea, decreased estradiol levels and increased gonadotrophin levels. Most cases of POI remain unresolved even after exhaustive investigations and is a significant cause of infertility in women in the reproductive age. In this study a total of 276 subjects, of which 138 POI patients and 138 controls were analysed for biochemical profiles of FSH, LH and Estradiol. Genotypic frequencies were calculated for different models of the SNP rs1256049 and rs4986938 in the Estrogen receptor Beta gene by PCR-RFLP (Restriction length polymorphism) analysis. Statistically, significant relation is found for FSH, LH and Estradiol profiles of a different group of Premature ovarian insufficiency and controls (p<0.0001). Genotypic frequencies between patients and controls were compared, and strength of the interdependence of genotypes and POI is confirmed by the odds ratio and 95% confidence intervals. Incidence of 1082 G>A (rs1256049) polymorphisms and 1730 G>A (rs4986938) were not significantly different in both patient and control group (P=0.21 and P=0.4). The presence of 1082 G>A (rs1256049) polymorphisms and 1730 G>A (rs4986938) is not associated with causation of Premature ovarian insufficiency in south Indian women.