Risk assessment for preeclampsia by biochemical and biophisycal markers at first trimester / Монголын Анагаах Ухаан

Introduction@#Preeclampsia, which affects about 2-8% of pregnancies, is major cause of maternal and perinatal morbidity and mortality, particularly in developing countries. In Mongolia, preeclampsia and eclampsia occurred among pregnancy complications about 25% in recent years. There is a percentage for a cause of maternal death was 17.7% in preeclampsia and eclampsia between 2012 and 2015 in Mongolia.</br> Effective prediction of preeclampsia can be achieved at 11-13 week’s gestation by combination of maternal characteristics, mean arterial pressure (MAP), uterine artery pulsatility index (UtA PI), maternal serum placental growth factor (PlGF), and pregnancy-associated plasma protein-A (PAPP-A).@*Goal@#To investigate plasma concentration of PIGF and PAPP-A, in pregnant women at 11-13+6 of gestation for screening of preeclampsia, To examine the performance of first-trimester screening for preeclampsia based on maternal characteristics, MAP, and mUt.A-PI.@*Materials and Methods @#The study conducted among 393 single pregnant women at 11-13+6 weeks, who were visiting antenatal care services, between March, 2015 and June, 2017. The prospective Cohort research method was used for this study. Written informed consent was obtained from all participants. Maternal plasma PAPP-A, PlGF were determined using Perkin Elmer kits by fluoroimmunoassay.</br> Measurement of MAP was by validated automated devices (HEM-7120, Оmron, Japan). MAP was calculated from the formula DP + 1/3*(SP-DP), where DP represents diastolic blood pressure and SP- systolic blood pressure. Trans-abdominal ultrasound (Voluson E8, GE, USA) examination was carried out for Ut.A-PI.@*Results@#In the study population, there were 66 (16.8%) cases that experienced preeclampsia and 327 (83.2%) cases that were unaffected by preeclampsia. The result showed that the mean concentration of PlGF was 38.6±19.6 pg/ml in PE group whereas the mean was 45.1±24.0 pg/ml in normal pregnant women. Level of PAPP-A was 366.1±195.3 mU/L in group with PE, 633.6±496.9 mU/L in group without preeclampsia. </br> The best Youden’s index and area under the curve (AUC) for MAP and mUt.A-PI were as a predictor of PE. It can be shown that the cutoff point for MAP was 89.5 mmHg (sensitivity-71.2%; specificity-75.5% J-0.467; AUC-0.792; P<0.001). The cutoff point of mUt.A-PI was 2.34 (sensitivity-33.3%; specificity-77.7% J-0.12; AUC-0.577; P<0.001).@*Conclusions@#The concentration of PIGF and PAPP-A in pregnant women with preeclampsia at 11-13+6 of gestation was lower than normal pregnant women. The detection risk of PE by MAP is more accurate than the mUtA-PI measurement.

Serum leptin level in Mongolian people with metabolic syndromee / Монголын Анагаах Ухаан

BackgroundLeptin is a mediator of long-term regulation of energy balance, suppressing food intake and therebyinducing weight loss.GoalThe main goal of our study was the analyzing of serum leptin level in correlation with some influencingfactors in adults with metabolic syndrome.Materials and MethodsWe included 260 randomly selected people aged 18-72 years old; among them 105 had metabolicsyndrome which was identified by the criteria of the International Diabetes Federation. All participantsunderwent general medical examinations and signed a written consent paper. Fasting blood glucose,triglyceride, HDL-C, insulin, adiponectin, leptin level were measured in fasting blood serum and insulinresistance was calculated as a HOMA-IR model.ResultsAverage level of leptin for participants with MS was 16.44±14.21ng/ml, in participants without MS was9.59±12.69ng/ml. MS exposed group had much higher level of leptin than the control group (p<0.001).Leptin level was correlated with waist circumference (β=-0.253±0.1; p=0.013), and body mass index(β=1.778±0.274; p<0.001).ConclusionLeptin level in the MS exposed group were higher than in the control group. The level of leptin had aconsistent and significant correlation with body mass index and waist circumference in compare to otherinfluencing factors.

The study of PGC-1α gene Gly482Ser polymorphism in people with metabolic syndrome in relation to risk factors of MS / Монголын Анагаах Ухаан

Introduction: The metabolic syndrome (MS) is characterized by central obesity, hypertriglyceridemia,low high-density lipoprotein (HDL), increase blood pressure and raise fasting plasma glucose. ThePGC-1α gene is located on chromosome 4 p.15.1 in humans and encodes a protein containing 798amino acids. The protein encoded by this gene is a transcriptional coactivator that regulates thegenes involved in energy metabolism. PPARγ, a coactivator molecule recently identified based on itsability to interact with PPARγ, is involved in many important metabolic processes, including adaptivethermogenesis, mitochondrial biogenesis and fatty acid β–oxidation.Goal: To study the frequency of PGC-1α Gly482Ser polymorphism in people with MS in relation to therisk factors of the MS.Materials and methods: The study population comprised 302 unrelated Mongolian subjects (158 withmetabolic syndrome and 144 controls). The genotypes for polymorphism of candidate gene related toMS were determined using a RFLP analysis of the MspI digest of the PCR product.Result: From the control group, 33.4% (48) had GG, 47.2% (68) had GS and 19.4% (28) had SSgenotypes. 51.9% (82) of people with MS had GG, 35.4% (56) had GS and 12.7% (20) had SSgenotypes. The prevalence of G allele in people with MS was 69.6%, which is much higher than healthygroup. Comparing PGC-1α Gly482Ser GG, GS and SS genotypes with systolic arterial blood pressurerevealed statistically significant difference which was higher among subjects with GG genotype. Theblood pressure of people with MS and carrying GG genotype of PGC-1α Gly482Ser polymorphismwas significantly increased 2.35 times than people without MS.Conclusions:1. 69.6 percentages of the people with MS had G allele and 2.2 times more than those withoutmetabolic syndrome.2. We determined that the odds ratio for the high blood pressure and it was 2.35 times higher inpeople with GG allele of Gly482Ser carriers than GS and SS alleles carriers (OR = 2.35, p =0.012).

11377C>G polymorphism of adipoq gene is associated with plasma tag level in people with metabolic syndrome / Монголын Анагаах Ухаан

Introduction. The metabolic syndrome is related to increased risk of developing cardiovascular disease andtype 2 diabetes. Adiponectin is an adipose tissue-specific collagen-like factor, which is abundant in plasma, anda decrease of adiponectin is associated with obesity and type-2 diabetes.Goal. This study aimed to determine the ADIPOQ gene -11377 polymorphism in association with plasmaadiponectin level and risk factors of metabolic syndrome.Materials and Methods. We investigated adiponectin gene -11377C>G polymorphism in 156 subjects withmetabolic syndrome and 142 healthy control subjects. The -11377C>G polymorphic locus was amplified using theforward primer 5’-ACTTGCCCTGCCTCTGTCTG-3’ and the reverse primer, 5-CCTGGAGAACTGGAAGCTG-3’.A p value G had lower levels of serum adiponectin than those with the genotype CC (7.38±3.68ng/ml) butno significant difference in people with MS (p=0.157). Therefore with genotype CG and GG (168.56±113.31mg/dl) of -11377C>G had higher levels of serum triglycerides than those with the genotype CC (132.94±74.78mg/dl) significant difference in people with MS (OR=1.006, p=0.015). With CG and GG (75.04±12.49mg/dl) of-11377C>G had significantly higher glucose level compared to with the genotype CC (68.85±11.76mg/dl) inwithout MS (OR=1.071, p=0.017).Сonclusions.1. ADIPOQ gene -11377>G polymorphism of the adiponectin gene was found not to be related to adiponectinlevel (p=0.157).2. -11377C>G polymorphism was related to the metabolic syndrome susceptibility, and this polymorphismimpacted on circulating triglyceride and glucose concentrations.

The study of PGC-1 gene polymorphism in relation with insulin resistance in people with metabolic syndrome / Монголын Анагаах Ухаан

INTRODUCTION: The PGC-1 gene is located on chromosome 4 p.15.1 in humans and encodes a protein containing 798 amino acids. As PGC-1a regulates multiple aspects of energy metabolism, it is not surprising that PGC-1a has been found to be deregulated in several pathological conditions. Might be associated with type 2 diabetes because PGC-1, besides being a coactivator of PPAR a and b, has a critical role in glucose uptake and adaptive thermogenesis. Addition, a common polymorphism of the PGC-1 gene Gly482Ser, which apparently reduces PGC-1 activity, has been linked to increased risk of type 2 diabetes. Association has also been reported between the Gly482Ser substitution and insulin resistance in Japanese subjects. Similar reduction of PGC-1 expression was also observed in the adipose tissue of insulin-resistant and morbidly obese individuals. Previous studies have reported significant association between the Gly482Ser missense mutation of the PGC-1 gene and reduced insulin sensitivity in obese subjects. This association resulted independent from all other known modulators of insulin resistance, and suggests a primary role for the PGC-1 gene on the genetic susceptibility to insulin resistance in obesity.GOAL: To study the presence of PGC-1 gene Gly482Ser polymorphism in people with Metabolic syndrome and study the relation to serum insulin level and insulin resistance.MATERIALS AND METHODS: The study population comprised 302 unrelated Mongolian subjects (158 with metabolic syndrome and 144 controls). MS was determined by IDF (International Diabetes Federation) criteria. The genotypes for polymorphism of candidate gene related to MS were determined using a RFLP analysis of the MspI digest of the PCR product. We determined serum insulin by ELISA, using Eucardio Company’s kit and insulin resistance was defined by the HOMA-IR formula.RESULT: 33.4% (48) of control group had GG, 47.2% (68) had GS and 19.4% (28) had SS genotypes of PGC-1 gene. 51.9% (82) of people with MS had GG, 35.4% (56) had GS and 12.7% (20) had SS genotypes. The prevalence of G allele in people with MS was 69.6%, which is much higher than healthy group. Insulin and HOMA-IR of MS group were higher than compared to healthy group (p<0.05). HOMA-IR was lower in people with GS genotype comparing to GG and SS in people with metabolic syndrome. CONCLUTIONS: 1. People with MS had higher levels of serum insulin (p<0.013) and insulin resistance (p<0.004) in compare to healthy people. 2. 69.6 percentages of the people with MS had G allele, which was 2.2 times more than those without metabolic syndrome.3. People with MS who carry SS genotype had higher levels of serum insulin (p=0.02) and insulin resistance (p=0.008) than people without MS. Insulin resistance was significantly correlated (r=0.302, p<0.001) with hypertension in people with G allele.

The study of apolipoprotein a5 gene polymorphisms in relation tolipidslevel in people with metabolic syndrome / Монголын Анагаах Ухаан

Background: Epidemiologic studies have shown a higher prevalenceof hypertriglyceridemia among patients with CHDthan among unaffected populations. Dozens of polymorphisms in different genesthat could have some effect on plasma TG levels havebeen analyzed. The most promising results are connected withvariants within the apolipoproteins (APO) APOA1/APOC3/ APOA4 gene cluster. Transgenic mice overexpressing human apolipoprotein A5decreased plasma triglyceride concentrations to one-third of those in control mice; conversely, knockout mice lacking APOA5 had four times as much plasma triglycerides as controls.The human APOA5 gene consistsof 4 exons and codes 369 aminoacidprotein, which is expressed almost exclusively in the liver.A minor allele of APOA5 (1259C, IVS3+476A and 1131C) which was independently associated with high plasma triglyceride levels in African-American, non Hispanic whites, Hispanic, Caucasians and Japanese were reported. Four polymorphisms in ApoA5 (1259T>C, IVS3+476G>A, S19W and 1131T>C) has been correlatedwith high TG levels in diabetic women. Materials and Methods: 162 people with MS for case group and 144 people for control group were selected in this study. MS was diagnosed according to IDF criteria and serum triglyceride, total cholesterol and HDL levels were determined. DNA from both case and control subjects were extracted from blood samples (20μL) using “G-spin™ Total DNA Extraction Kit”(iNtRON Biotechnology, Inc).The genotypes for fourpolymorphisms of ApoA5 were determined using a combination of PCR and sequence-specific oligonucleotide probes. Results: There were 304 total subjects included males 50.3% (153) and female 49.7% (151) in our study. The appearance of risk genotypes of 1177C>T, 1259T>C, IVS3+476G>A and 1131T>C polymorphisms in ApoA5 gene were higher in MS group than control group.Serum levels of triglycerides and total cholesterol differed significantly (pC genotypes. Conclusion: TAG and TC level was higher in people with 1131T>C-CC genotype than other genotypes in both groups (p=0.010, p=0.001). We determined that the odds ratio for the hypertriglyceridemia was 5.98 for ApoA5-1131T>C CC-genotype carriers.

The study of apolipoprotein A5 gene polymorphism in relation to serum triglyceride level in people with metabolic syndrome / Монголын Анагаах Ухаан

Background. A large number of longitudinal studies indicate significantly increased risk of cardiovascular events and death in people with the MetSyn and high plasma levels of triglycerides are an independent risk factor for the development of cardiovascular disease. Apolipoprotein A5 (APOA5) gene, a new member of the APOA1/C3/A4 gene cluster, was identified by comparative sequencing of human and mice DNA by Pennacchio and co-workers in 2001. Since this discovery, variants of ApoA5 gene have been independently assiociated with level of plasma triglyceride in many countries. Human ApoA5 is expressed in the liver then appears in plasma in association with VLDL and HDL and plays a major role in TG catabolism. Variant at ApoA5 gene locus, 1177C>T is located in 3’ UTR which often contains regulatory regions that influence post-transcriptional gene expression. One alteration can be responsible for the altered expression of many genes. Materials and Methods. 152 people with MS for case group and 152 people for control group were selected in this study. MS was diagnosed according to IDF criteria and serum triglyceride levels were determined. DNA from both case and control subjects were extracted from blood samples (200 ml) using “G-spin™ Total DNA Extraction Kit”(iNtRON Biotechnology, Inc). To detect the 1177C>T variation of ApoA5 gene, using High Pure PCR Template Preparation Kits, a forward primer 5’-CTCTGAGCCTCTAGCATGGTTGAGT- 3’ and the mismatch reverse primer 5’-GAGCATTCCCAAATGAGCAC-3’ were used to create the HinfI restriction site. Results. There were 304 total subjects included males 50.3% (153) and female 49.7% (151) in our study. Incident of CC genotype was 71.1% (216), CT genotype was 25% (76) and TT genotype was 3.9%, TAG level was higher in males than females in both groups (p=0.016, ð=0.001) for CC genotype and also, higher with MS in males for CT genotype (p=). But, TAG level was no significant difference among three genotypes in group with MS subjects (male p=0.236, female p=0.881). Conclusion: The TT genotype of the ApoA5 gene 1177C>T polymorphism frequency was 2.9% in control subjects and 4.9% in subjects with MS. However, TG level was not differ in both groups for TT genotype, TAG level in males was higher compared with females (p=0.016 in control, p=0.001 in group with MS).