Browsing by Author "Kalnina, Ineta"

Now showing 1 - 7 of 7
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    Genomic Characterization and Initial Insight into Mastitis-Associated SNP Profiles of Local Latvian Bos taurus Breeds
    (2023) Gudrā, Dita; Valdovska, Anda; Jonkus, Daina; Galina, Daiga; Kairisa, Daina; Ustinova, Maija; Vīksne, Kristīne; Fridmanis, Davids; Kalnina, Ineta; Scientific Laboratory of Molecular Genetics
    Latvia has two local Bos taurus breeds—Latvian Brown (LBG) and Latvian Blue (LZG)—characterized by a good adaptation to the local climate, longevity, and high fat and protein contents in milk. Since these are desired traits in the dairy industry, this study investigated the genetic background of the LBG and LZG breeds and identified the genetic factors associated with mastitis. Blood and semen samples were acquired, and whole genome sequencing was then performed to acquire a genomic sequence with at least 35× or 10× coverage. The heterozygosity, nucleotide diversity, and LD analysis indicated that LBG and LZG cows have similar levels of genetic diversity compared to those of other breeds. An analysis of the population structure revealed that each breed clustered together, but the overall differentiation between the breeds was small. The highest genetic variance was observed in the LZG breed compared with the LBG breed. Our results show that SNP rs721295390 is associated with mastitis in the LBG breed, and SNPs rs383806754, chr29:43998719CG>C, and rs462030680 are associated with mastitis in the LZG breed. This study shows that local Latvian LBG and LZG breeds have a pronounced genetic differentiation, with each one suggesting its own mastitis-associated SNP profile.
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    Genomic diversity of the locally developed Latvian Darkheaded sheep breed
    (2024-05-01) Gudra, Dita; Valdovska, Anda; Kairisa, Daina; Galina, Daiga; Jonkus, Daina; Ustinova, Maija; Viksne, Kristine; Kalnina, Ineta; Fridmanis, Davids
    The Latvian Darkheaded is the only locally developed sheep breed. The breed was formed at the beginning of the 20th century by crossing local coarse-wooled sheep with the British Shropshire and Oxfordshire breeds. The breed was later improved by adding Ile-de-France, Texel, German blackheads, and Finnsheep to achieve higher prolificacy and better meat quality. Previous studies have reported the Latvian Darkheaded sheep to be closely related to Estonian and Lithuanian Blackface breeds, according to microsatellite data. To expand our knowledge of the genetic resources of the Latvian Darkheaded breed, we conducted a whole-genome resequencing analysis on 40 native sheep. The investigation showed that local sheep harbor genetic diversity levels similar to those observed among other improved breeds of European origin, including Charollais and Suffolk. Genome-wide nucleotide diversity (π) in Latvian Darkheaded sheep was 3.91 × 10−3, whereas the average observed heterozygosity among the 40 animals was 0.267 and 0.438 within the subsample of unrelated individuals. The Ne has rapidly decreased to 200 ten generations ago with a recent drop to Ne 73 four generations ago. However, inbreeding levels based on runs of homozygosity were, on average, low, with FROH ranging between 0.016 and 0.059. The analysis of the genomic composition of the breed confirmed shared ancestry with sheep of British origin, reflecting the history of the breed. Nevertheless, Latvian Darkheaded sheep were genetically separable. The contemporary Latvian Darkheaded sheep population is genetically diverse with a low inbreeding rate. However, further development of breed management programs is necessary to prevent an increase in inbreeding, loss of genetic diversity, and depletion of breed-specific genetic resources, ensuring the preservation of the native Latvian Darkheaded sheep.
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    Metformin strongly affects transcriptome of peripheral blood cells in healthy individuals
    (2019-11-01) Ustinova, Monta; Silamikelis, Ivars; Kalnina, Ineta; Ansone, Laura; Rovite, Vita; Elbere, Ilze; Radovica-Spalvina, Ilze; Fridmanis, Davids; Aladyeva, Jekaterina; Konrade, Ilze; Pirags, Valdis; Klovins, Janis; Rīga Stradiņš University
    Metformin is a commonly used antihyperglycaemic agent for the treatment of type 2 diabetes mellitus. Nevertheless, the exact mechanisms of action, underlying the various therapeutic effects of metformin, remain elusive. The goal of this study was to evaluate the alterations in longitudinal whole-blood transcriptome profiles of healthy individuals after a one-week metformin intervention in order to identify the novel molecular targets and further prompt the discovery of predictive biomarkers of metformin response. Next generation sequencing-based transcriptome analysis revealed metformin-induced differential expression of genes involved in intestinal immune network for IgA production and cytokine-cytokine receptor interaction pathways. Significantly elevated faecal sIgA levels during administration of metformin, and its correlation with the expression of genes associated with immune response (CXCR4, HLA-DQA1, MAP3K14, TNFRSF21, CCL4, ACVR1B, PF4, EPOR, CXCL8) supports a novel hypothesis of strong association between metformin and intestinal immune system, and for the first time provide evidence for altered RNA expression as a contributing mechanism of metformin’s action. In addition to universal effects, 4 clusters of functionally related genes with a subject-specific differential expression were distinguished, including genes relevant to insulin production (HNF1B, HNF1A, HNF4A, GCK, INS, NEUROD1, PAX4, PDX1, ABCC8, KCNJ11) and cholesterol homeostasis (APOB, LDLR, PCSK9). This inter-individual variation of the metformin effect on the transcriptional regulation goes in line with well-known variability of the therapeutic response to the drug.
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    Significantly altered peripheral blood cell DNA methylation profile as a result of immediate effect of metformin use in healthy individuals
    (2018-12-13) Elbere, Ilze; Silamikelis, Ivars; Ustinova, Monta; Kalnina, Ineta; Zaharenko, Linda; Peculis, Raitis; Konrade, Ilze; Ciuculete, Diana Maria; Zhukovsky, Christina; Gudra, Dita; Radovica-Spalvina, Ilze; Fridmanis, Davids; Pirags, Valdis; Schiöth, Helgi B.; Klovins, Janis
    Background: Metformin is a widely prescribed antihyperglycemic agent that has been also associated with multiple therapeutic effects in various diseases, including several types of malignancies. There is growing evidence regarding the contribution of the epigenetic mechanisms in reaching metformin's therapeutic goals; however, the effect of metformin on human cells in vivo is not comprehensively studied. The aim of our study was to examine metformin-induced alterations of DNA methylation profiles in white blood cells of healthy volunteers, employing a longitudinal study design. Results: Twelve healthy metformin-naïve individuals where enrolled in the study. Genome-wide DNA methylation pattern was estimated at baseline, 10 h and 7 days after the start of metformin administration. The whole-genome DNA methylation analysis in total revealed 125 differentially methylated CpGs, of which 11 CpGs and their associated genes with the most consistent changes in the DNA methylation profile were selected: POFUT2, CAMKK1, EML3, KIAA1614, UPF1, MUC4, LOC727982, SIX3, ADAM8, SNORD12B, VPS8, and several differentially methylated regions as novel potential epigenetic targets of metformin. The main functions of the majority of top-ranked differentially methylated loci and their representative cell signaling pathways were linked to the well-known metformin therapy targets: regulatory processes of energy homeostasis, inflammatory responses, tumorigenesis, and neurodegenerative diseases. Conclusions: Here we demonstrate for the first time the immediate effect of short-term metformin administration at therapeutic doses on epigenetic regulation in human white blood cells. These findings suggest the DNA methylation process as one of the mechanisms involved in the action of metformin, thereby revealing novel targets and directions of the molecular mechanisms underlying the various beneficial effects of metformin. Trial registration: EU Clinical Trials Register, 2016-001092-74. Registered 23 March 2017, https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-001092-74/LV.
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    Single nucleotide polymorphisms in the intergenic region between metformin transporter OCT2 and OCT3 coding genes are associated with short-Term response to metformin monotherapy in type 2 diabetes mellitus patients
    (2016-12) Zaharenko, Linda; Kalnina, Ineta; Geldnere, Kristine; Konrade, Ilze; Grinberga, Solveiga; Židzik, Jozef; Javorský, Martin; Lejnieks, Aivars; Nikitina-Zake, Liene; Fridmanis, Davids; Peculis, Raitis; Radovica-Spalvina, Ilze; Hartmane, Dace; Pugovics, Osvalds; Tká, Ivan; Klimáková, Lucia; Pirags, Valdis; Klovins, Janis; Rīga Stradiņš University
    Objective(s): High variability in clinical response to metformin is often observed in type 2 diabetes (T2D) patients, and it highlights the need for identification of genetic components affecting the efficiency of metformin therapy. Aim of this observational study is to evaluate the role of tagSNPs (tagging single nucleotide polymorphisms) from genomic regions coding for six metformin transporter genes with respect to the short-Term efficiency. Design: 102 tagSNPs in 6 genes coding for metformin transporters were genotyped in the group of 102 T2D patients treated with metformin for 3 months. Methods: Most significant hits were analyzed in the group of 131 T2D patients from Slovakia. Pharmacokinetic study in 25 healthy nondiabetic volunteers was conducted to investigate the effects of identified polymorphisms. Results: In the discovery group of 102 patients, minor alleles of rs3119309, rs7757336 and rs2481030 were significantly nominally associated with metformin inefficiency (P = 1.9 × 106 to 8.1 × 106). Effects of rs2481030 and rs7757336 did not replicate in the group of 131 T2DM patients from Slovakia alone, whereas rs7757336 was significantly associated with a reduced metformin response in combined group. In pharmacokinetic study, group of individuals harboring risk alleles of rs7757336 and rs2481030 displayed significantly reduced AUC∞ of metformin in plasma. Conclusions: For the first time, we have identified an association between the lack of metformin response and SNPs rs3119309 and rs7757336 located in the 5 flanking region of the genes coding for Organic cation transporter 2 and rs2481030 located in the 5 flanking region of Organic cation transporter 3 that was supported by the results of a pharmacokinetic study on 25 healthy volunteers.
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    Variations in the Relative Abundance of Gut Bacteria Correlate with Lipid Profiles in Healthy Adults
    (2023) Kalnina, Ineta; Gudrā, Dita; Silamikelis, Ivars; Vīksne, Kristīne; Roga, Ance; Skinderskis, Edmunds; Fridmanis, Davids; Kloviņš, Jānis
    The gut microbiome is a versatile system regulating numerous aspects of host metabolism. Among other traits, variations in the composition of gut microbial communities are related to blood lipid patterns and hyperlipidaemia, yet inconsistent association patterns exist. This study aims to assess the relationships between the composition of the gut microbiome and variations in lipid profiles among healthy adults. This study used data and samples from 23 adult participants of a previously conducted dietary intervention study. Circulating lipid measurements and whole-metagenome sequences of the gut microbiome were derived from 180 blood and faecal samples collected from eight visits distributed across an 11-week study. Lipid-related variables explained approximately 4.5% of the variation in gut microbiome compositions, with higher effects observed for total cholesterol and high-density lipoproteins. Species from the genera Odoribacter, Anaerostipes, and Parabacteroides correlated with increased serum lipid levels, whereas probiotic species like Akkermansia muciniphila were more abundant among participants with healthier blood lipid profiles. An inverse correlation with serum cholesterol was also observed for Massilistercora timonensis, a player in regulating lipid turnover. The observed correlation patterns add to the growing evidence supporting the role of the gut microbiome as an essential regulator of host lipid metabolism.
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    A widely used sampling device in colorectal cancer screening programmes allows for large-scale microbiome studies
    (2019-09-01) Gudra, Dita; Shoaie, Saeed; Fridmanis, Davids; Klovins, Janis; Wefer, Hugo; Silamikelis, Ivars; Peculis, Raitis; Kalnina, Ineta; Elbere, Ilze; Radovica-Spalvina, Ilze; Hultcrantz, Rolf; Škenders, Girts; Leja, Marcis; Engstrand, Lars