0000000000542964
AUTHOR
Monta Ustinova
First Report on the Latvian SARS-CoV-2 Isolate Genetic Diversity
Remaining a major healthcare concern with nearly 29 million confirmed cases worldwide at the time of writing, novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused more than 920 thousand deaths since its outbreak in China, December 2019. First case of a person testing positive for SARS-CoV-2 infection within the territory of the Republic of Latvia was registered on 2nd of March 2020, 9 days prior to the pandemic declaration by WHO. Since then, more than 277,000 tests were carried out confirming a total of 1,464 cases of coronavirus disease 2019 (COVID-19) in the country as of 12th of September 2020. Rapidly reacting to the spread of the infection, an ongoing sequenci…
Epigenetic markers associated with metformin response and intolerance in drug-naïve patients with type 2 diabetes
Metformin is the first-line pharmacotherapy for managing type 2 diabetes (T2D). However, many patients with T2D do not respond to or tolerate metformin well. Currently, there are no phenotypes that successfully predict glycemic response to, or tolerance of, metformin. We explored whether blood-based epigenetic markers could discriminate metformin response and tolerance by analyzing genome-wide DNA methylation in drug-naïve patients with T2D at the time of their diagnosis. DNA methylation of 11 and 4 sites differed between glycemic responders/nonresponders and metformin-tolerant/intolerant patients, respectively, in discovery and replication cohorts. Greater methylation at these sites associ…
KRAS gēna varianta rs61764370 ietekme uz saslimšanu ar krūts vēzi un pacientu dzīvildzi
Ģenētiskie marķieri, to skaitā viena nukleotīda nomaiņas, ir aktuāls pētījumu objekts krūts vēža patoģenēzē. KRAS gēnā lokalizētais sekvences variants rs61764370 ir jauns biomarķieris, kura klīniskā nozīme audzēju attīstībā pagaidām nav skaidra. Datu par rs61764370 ietekmi uz krūts vēža attīstību un prognozi ir salīdzinoši maz, tāpēc bakalaura darba mērķis bija noteikt rs61764370 ietekmi uz saslimšanu ar krūts vēzi un pacientu dzīvildzi. Pētījumā analizēja 2652 secīgo krūts vēža pacienšu un 861 praktiski veselu brīvprātīgo asins donoru DNS paraugus, kas izolēti no venozajām asinīm. Rs61764370 klātbūtni DNS paraugos noteica ar RFLP metodi, ko verificēja ar Sangera sekvenēšanu. Pieejamos klīn…
Whole-blood transcriptome profiling reveals signatures of metformin and its therapeutic response
Metformin, a biguanide agent, is the first-line treatment for type 2 diabetes mellitus due to its glucose-lowering effect. Despite its wide application in the treatment of multiple health conditions, the glycemic response to metformin is highly variable, emphasizing the need for reliable biomarkers. We chose the RNA-Seq-based comparative transcriptomics approach to evaluate the systemic effect of metformin and highlight potential predictive biomarkers of metformin response in drug-naive volunteers with type 2 diabetes in vivo. The longitudinal blood-derived transcriptome analysis revealed metformin-induced differential expression of novel and previously described genes involved in cholester…
Baseline gut microbiome composition predicts metformin therapy short-term efficacy in newly diagnosed type 2 diabetes patients
BackgroundThe study was conducted to investigate the effects of metformin treatment on the human gut microbiome's taxonomic and functional profile in the Latvian population, and to evaluate the correlation of these changes with therapeutic efficacy and tolerance.MethodsIn this longitudinal observational study, stool samples for shotgun metagenomic sequencing-based analysis were collected in two cohorts. The first cohort included 35 healthy nondiabetic individuals (metformin dose 2x850mg/day) at three time-points during metformin administration. The second cohort was composed of 50 newly-diagnosed type 2 diabetes patients (metformin dose-determined by an endocrinologist) at two concordant ti…
Multifaktoriāla krūts vēža ģenētisko riska faktoru izvērtējums
Krūts vēzis ir kompleksa, multifaktoriāla slimība, kurai raksturīga ārējās vides un ģenētisko riska faktoru mijiedarbība. Zemas penetrances alēliskie varianti ir aktuāls pētījumu objekts krūts vēža patoģenēzē. Ar krūts vēža attīstību saistītiem zemas penetrances variantiem ir novērots variabls sastopamības biežums un predispozīcijas efekta spēks starp dažādām populācijām. Šī pētījuma mērķis bija noteikt 11 zemas penetrances alēlisko variantu saistību ar krūts vēža attīstību Latvijas populācijā. Pētījumā analizēja 2609 krūts vēža pacienšu un 694 brīvprātīgo asins donoru genomisko DNS. Vienpadsmit alēlisko variantu genotipēšanu veica ar RFLP un TaqMan zondēm. Genotipēšanas rezultātus un pieej…