An insight into major signaling pathways and protein-protein interaction networks involved in the pathogenesis of gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is associated with the increase of glucose in the blood rather than being absorbed by the cells. A better understanding of the signaling pathways is necessary to understand the pathophysiology of GDM. This study provides details about a series of signaling pathways and protein-protein interactions involved in the pathogenesis of GDM and their evaluations in GDM development. Protein-protein interactions were found between proteins of several signaling pathways that suggest interlink between these signaling pathways. Protein-protein interactions were generated with high confidence interaction scores based on textmining, cooccurrence, coexpression, neighborhood, gene fusion, experiments, and databases. The dysregulation of signaling pathways may also contribute to the increased risk of complications associated with GDM in the mother and child. Further, studies on signaling pathways involved in the pathogenesis of GDM would help in the development of an effective intervention to prevent GDM along with the identification of key targets for effective therapies in the future.

Levothyroxine Dosing after Delivery in Women Diagnosed with Hypothyroidism During Pregnancy-A Retrospective, Observational Study.

BACKGROUND: Pregnancy leads to profound alteration in thyroid function and dysthyroidism contributes to adverse pregnancy outcomes. Though the management of hypothyroidism during pregnancy is highlighted, the same is often neglected during postpartum. We have evaluated the postpartum levothyroxine (LT4) dose change in patients with new onset hypothyroidism. METHODS: We conducted this retrospective, observational study between 2014 and 2016 using the medical records of patients with new onset hypothyroidism during pregnancy. We included patients who continued with LT4 after delivery (as per predetermined protocol) and the availability of 2-year follow up record. We excluded patients who stopped LT4 and use of other drugs that affect the thyroid function tests (TFT) after delivery. The patients were divided into 2 groups for comparison [Group 1-Overt hypothyroidism (OH) and Group 2-Subclinical hypothyroidism (SCH)] based on the initial TFT reports. The data were analyzed using appropriate statistical methods and a P value of less than 0.05 was considered significant. RESULTS: A total of 159 women continued using LT4 after delivery and the final follow up data were available for 130 patients only. LT4 dose up titration was observed more in group 1 than in group 2 (P = 0.0336). In both the groups, the presence of goitre, thyroid autoimmunity and a repeat pregnancy are associated with increasing LT4 requirement. CONCLUSION: Majority of patients with OH during pregnancy require more than half of the final dose after delivery. Goitre and autoimmunity are associated with higher LT4 dose after delivery.

Polymorphisms in the IRS-1 and PPAR-γ genes and their association with polycystic ovary syndrome among South Indian women.

Polycystic ovary syndrome is known to be characterized by metabolic abnormalities such as hyperinsulinemia, adiposity and dyslipidemia. Both insulin receptor substrate-1 and peroxisome proliferator-activated receptor-γ have emerged as significant candidate genes in the pathogenesis of PCOS. In this study, we report for the first time, the association pattern of these genes with PCOS among South Indian women. Two hundred fifty PCOS cases and 299 controls were sequenced for IRS-1 exon1 and PPAR-γ exon 2 and exon 6 to study the already reported SNPs in other ethnic groups and to identify any novel SNP in these exonic regions specific to the Indian population. We did not find any novel SNP in our population except for those already reported- two IRS-1 polymorphisms (Gly972Arg and G2323A) and two PPAR-γ polymorphisms (Pro12Ala and His447His). While the IRS-1 polymorphic alleles had a similar distribution between cases and controls, the PPAR-γ exon 2 Ala allele and exon 6 His447His T allele were significantly more in the controls than in the cases (p≤0.05). Haplotype association analysis also suggests that both IRS-1 and PPAR-γ haplotypes with mutations depicted reduced frequency of hyperandrogenic and metabolic traits in PCOS compared to the haplotype with only wild type alleles. Our study on Indian women suggests that while IRS-1, contrary to the earlier findings in other ethnic groups, seems to have a probable protective role against development of specific PCOS sub-phenotypes, the evidence for a probable protective role of PPAR-γ is reaffirmed in our study.

Association of CAPN10 SNPs and haplotypes with polycystic ovary syndrome among South Indian Women.

Polycystic Ovary Syndrome (PCOS) is known to be characterized by metabolic disorder in which hyperinsulinemia and peripheral insulin resistance are central features. Given the physiological overlap between PCOS and type-2 diabetes (T2DM), and calpain 10 gene (CAPN10) being a strong candidate for T2DM, a number of studies have analyzed CAPN10 SNPs among PCOS women yielding contradictory results. Our study is first of its kind to investigate the association pattern of CAPN10 polymorphisms (UCSNP-44, 43, 56, 19 and 63) with PCOS among Indian women. 250 PCOS cases and 299 controls from Southern India were recruited for this study. Allele and genotype frequencies of the SNPs were determined and compared between the cases and controls. Results show significant association of UCSNP-44 genotype CC with PCOS (p = 0.007) with highly significant odds ratio when compared to TC (OR = 2.51, p = 0.003, 95% CI = 1.37-4.61) as well as TT (OR = 1.94, p = 0.016, 95% CI = 1.13-3.34). While the haplotype carrying the SNP-44 and SNP-19 variants (21121) exhibited a 2 fold increase in the risk for PCOS (OR = 2.37, p = 0.03), the haplotype containing SNP-56 and SNP-19 variants (11221) seems to have a protective role against PCOS (OR = 0.20, p = 0.004). Our results support the earlier evidence for a possible role of UCSNP-44 of the CAPN10 gene in the manifestation of PCOS.

Androgen receptor CAG repeat polymorphism and epigenetic influence among the south Indian women with Polycystic Ovary Syndrome.

The present study was carried out to assess the role of androgen receptor CAG repeat polymorphism and X chromosome inactivation (XCI) pattern among Indian PCOS women and controls which has not been hitherto explored and also to test the hypothesis that shorter CAG alleles would be preferentially activated in PCOS. CAG repeat polymorphism and X chromosome methylation patterns were compared between PCOS and non-PCOS women. 250 PCOS women and 299 controls were included for this study. Androgen receptor CAG repeat sizes, XCI percentages, and clinical and biochemical parameters were measured. The mean CAG repeat number is similar between the cases (18.74±0.13) and controls (18.73±0.12). The obese PCOS women were significantly more frequent in the <18 and >20 CAG repeat category than the lean PCOS women, yielding a highly significant odds (p=0.001). Among the women with non-random X-inactivation, alleles with <19 repeats were more frequently activated among cases than controls (p=0.33). CAG repeat polymorphism by itself cannot be considered as a useful marker for discriminating PCOS. We observed a trend of preferential activation of the shorter allele among the PCOS cases with non random XCI pattern. In the obese PCOS women, this microsatellite variation may account for the hyperandrogenicity to a larger extent than the lean PCOS women.