The frequency of familial hypercholesterolemia amongst patients in the outpatient clinic of the tertiary specialized cardiology center in Kyrgyzstan.

BACKGROUND: Familial hypercholesterolemia (FH) is frequently underdiagnosed. Prevalence of the FH in Kyrgyzstan is unknown. AIM: to investigate the prevalence of FH amongst patients in the outpatient settings of the tertiary cardiologic center in Kyrgyzstan. METHODS: Retrospective observational study was conducted using the database of the laboratory of biochemistry and electronic database of outpatient department of the National Center of Cardiology and internal diseases. Patient with the level of total cholesterol (TC) ≥7,5 mmol/l and/or low density lipoprotein cholesterol (LDL-C) ≥ 4,9 mmol/l without signs of secondary hyperlipidemia were included in the analysis. FH was defined using Dutch Lipid Clinic Network criteria. RESULTS: according to the laboratory database levels of TC and LDL-C was conducted in 8281patiens and 525 of them had a high lipid levels. After exclusion of patients with secondary hyperlipidemia, high level of triglycerides and pregnant women - 91 patients were included in the analysis. Among them the definite FH was revealed in 2 (2,2%) patients, probable FH - in 6 (6,6%), and possible in 76 (83,5%), and in 7,7% there were no signs of FH. CONCLUSION: Frequency of potential FH (definite and probable) in our analysis was low. To understand the real prevalence of FH in a Kyrgyz population epidemiological study is needed.

[Risk of type 2 diabetes mellitus in the Kyrgyz population in the presence of ADIPOQ (G276T), KCNJ11 (Glu23Lys), TCF7L2 (IVS3C>T) gene polymorphisms]. / Risk razvitiia sakharnogo diabeta 2-go tipa v kyrgyzskoi populiatsii pri nalichii polimorfizmov G276T gena ADIPOQ, Glu23Lys gena KCNJ11 i IVS3C>T gena TCF7L2.

AIM: To analyze the association of genotype combinations of the polymorphic markers G276T in the ADIPOQ gene, Glu23Lys in the KCNJ11 gene, and IVS3C>T in the TCF7L2 gene with the development of type 2 diabetes mellitus (T2DM) in the Kyrgyz population. SUBJECTS AND METHODS: The investigation enrolled 23 Kyrgyz people, of whom there were 114 patients with T2DM and 109 without T2DM (a control group). T2DM was diagnosed in accordance with the WHO criteria (1999). The genotypes of ADIPOQ (G276T), KCNJ11 (Glu23Lys), and TCF7L2 (IVS3C>T) gene polymorphisms were identified using the restriction fragment length polymorphism analysis. RESULTS: When typing at the polymorphic loci G276T in the ADIPOQ gene, Glu23Lys in the KCNJ11 gene, and IVS3C>T in the TCF7L2 gene, the development of T2DM in the Kyrgyz population was associated with the T allele (odds ratio (OR), 1.68; p=0.025), the heterozygous G276T genotype (OR 1,8; p=0.036) in the ADIPOQ gene; the 23Lys allele (OR, 1.62; p=0.019) in the KCNJ11 gene; a two-locus genotype combination in the genes ADIPOQ/KCNJ11: G276T/Glu23Lys (OR, 4.88; p=0.0013), G276G/Lys23Lys (OR, 4.65; p=0.019), G276T/Glu23Glu (OR, 3.10; p=0.022), a two-locus genotype combination in the genes ADIPOQ/TCF7L2: G276T/СС (OR, 1.97; p=0.04); two-locus genotype combinations in the genes KCNJ11/TCF7L2: Lys23Lys/CC (ОR, 2.65; p=0.042), Glu23Lys/CT (OR, 3.88; p=0.027); and a three-locus genotype combination in the genes ADIPOQ/KCNJ11/TCF7L2: G276T/Glu23Lys/CT (OR, 14.48; p=0.02). CONCLUSION: The development of T2DM in the Kyrgyz population is genetically determined by ADIPOQ (G276T) gene, KCNJ11 (Glu23Lys), and TCF7L (IVS3C>T) gene polymorphisms with the predisposing value of the T allele of the heterozygous G276T genotype in the ADIPOQ gene; the 23Lys allele in the KCNJ1 gene; as well as by genotype combinations in the genes ADIPOQ/KCNJ11 (G276T/Glu23Lys, G276G/Lys23Lys, G276T/Glu23Glu); ADIPOQ/TCF7L2 (G276T/SS); KCNJ11/TCF7L2 (Lys23Lys/CC, Glu23Lys/CT); ADIPOQ/KCNJ11/TCF7L2 (G276T/Glu23Lys /CT). The IVS3C>T locus in the TCF7L2 gene is not independently statistically significantly associated with the development of T2DM; however, its predisposing effect has been identified in its combination with the variant genotypes of the polymorphic loci G276T in the ADIPOQ gene and Glu23Lys in the KCNJ11 gene.

[Association of the polymorphic marker Glu23Lys in the KCNJ11 gene with hypertension in Kyrgyz patients]. / Assotsiatsiia polimorfnogo markera Glu23Lys gena KCNJ11 s razvitiem arterial'noi gipertonii u patsientov kirgizskoi natsional'nosti.

AIM: To study the association of the polymorphic marker Glu23Lys in the KCNJ11 with the development of hypertension in Kyrgyz patients. SUBJECTS AND METHODS: This case-control study enrolled 214 unrelated ethnic Kyrgyzes, in which a study group included 152 hypertensive patients (82 men and 70 women) and a control group consisted of 109 apparently healthy individuals (61 men and 48 women). The examinees' mean age was 55.2±10.1 years. Hypertension was verified when blood pressure (BP) was above 140/90 mm Hg. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to identify the polymorphic marker Glu23Lys in the KCNJ11 gene. RESULTS: In the hypertension and control groups, the prevalence of 3 genotypes (Glu23Glu, Glu23Lys, and Lys23Lys) of the Glu23Lys polymorphism in the KCNJ11 gene differed significantly (χ2=8.04; p=0.018). The Lys23Lys and Glu23Lys genotypes were statistically more frequently recorded in the hypertension group and the homozygous Glu23Glu genotype was, on the contrary, more common in the control group than in the study one. In the hypertension group, the 23Lys allele frequency was statistically significantly higher than that in the control one (χ2=7.36; p=0.0067). The carriage of the 23Lys allele increased the risk of hypertension by 1.68 times (odds ratio (OR), 1.68; 95% confidence interval (CI), 1.17-2.41), that of the Glu23 allele had, on the contrary, a protective effect (OR, 0.60; 95% CI, 0.41-0.86). CONCLUSION: The polymorphic marker Glu23Lys in the KCNJ11 gene is associated with hypertension in the Kyrgyzes. The 23Lys allele is a marker for the higher risk of hypertension.

[An Association Between T455C Polymorphism of Apolipoprotein C-III Gene, Insulin Resistance and Metabolic Syndrome Components].

AIM: to study an association between T455C apolipoprotein C-III (apo C-III) gene polymorphism, insulin resistance (IR), metabolic syndrome (MS) and its components in a Kyrgyz ethnic group. MATERIAL AND METHODS: 259 persons: 162 patients with MS and 97 sex and age matched controls without MS, diabetes mellitus and cardiovascular diseases were included in the study. Clinical examination with arterial blood pressure, anthropometric data measurement and laboratory tests for blood glucose and lipid parameters were performed in all included persons. In 140 patients test for immunoreactive serum insulin was done. DNA was extracted from blood cells and T455C polymorphism of apo C-III gene was determined by PCR method. RESULTS: In examined persons the most frequent was TC genotype as in group with MS as in controls. The difference on genotype's frequency between group was close to significant level (χ2 =5.48; p = 0.06) and odd ratio (OR) for MS between CC and TT carriers was 2.57 (95% CI 1.15-5.72); p = 0.019). Frequency of 455C allele in control group was--0.44 and in group with MS--0.54 (χ2 = 4.55; p = 0.036). In carriers of CC genotype there was noted that the frequency of IR (61.8% vs 23.1% vs 36.3%; p < 0.005), insulin level (11.9 [7.04-16.3] vs 5.73 [3.34-10.3] vs 7.54 [4.59-12.2] µIU/ml; p < 0.01) and HOMA index (3.14 [1.66-4.79] vs 1.46 [0.8-2.6] vs 2.05 [1.12-3.6]; p < 0.01) were significantly higher compared with TT and TC genotypes groups respectively. OR for IR between CC and TT carriers was 5.39 (95% CI 1.7-16.9; p = 0.0028). There also was an association between CC genotype and other MS components such as abdominal obesity (χ2--6.24; p--0.044, OR (95% CI--2.21 [1.03-4.82]) and high level of blood triglycerides (χ2--7.57; p--0.022, OR (95% CI) 2.5 [1.14-5.5]). CONCLUSION: In examined Kyrgyz ethnic population the most frequent was heterozygous TC genotype of T455C polymorphism of apo C-III. An association of 455C allele and CC genotype with MS, IR, abdominal obesity and high level of triglycerides was revealed. Key words: apolipoprotein C-III; T455C gene polymorphism; metabolic syndrome, insulin resistance.

[Association of adiponectin gene G276T polymorphism with the development of metabolic syndrome in ethnic Kyrgyz patients]. / Assotsiatsiya polimorfnogo markera G276T gena adiponektina s razvitiem metabolicheskogo sindroma u patsientov kirgizskoi natsional'nosti.

AIM: To study the association of adiponectin gene G276Т (ADIPOQ) polymorphism with the development of metabolic syndrome (MS) in ethnic Kyrgyz patients. MATERIAL AND METHODS: A total of 171 patients with MS (a study group) and 117 patients without MS (a comparison group) were examined. MS was defined on the basis of the modified ATP III criteria. The genotypes of the G276T polymorphism in the adiponectin gene were determined by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: Dividing the MS and control groups by gender revealed statistically significant differences in the distribution of alleles and genotypes only among the women. There was a higher frequency of GT+TT genotypes (53% vs 34%; χ2=5.942; р=0.014) and T allele (30% vs 19%; χ2=4.489; р=0.0341) in the women with MS than in those without MS. Iin the ethnic Kyrgyz women, the T allele at the G276Т polymorphic locus in the ADIPOQ gene was associated with the development of MS (odds ratio (OR)=1.82; 95% confidence interval (CI) 1.04-3.19) and type 2 diabetes mellitus (T2DM) (OR=2.63; 95% CI, 1.05-6.56 ) with the high levels of leptin (p<0.05), glucose (p<0.05), triglycerides (OR=3.06; 95% CI, 1.05-8.93), low-density lipoprotein cholesterol (OR=2.80; 95% CI, 1,07-7.31) and with the lower level of high-density lipoprotein cholesterol (OR=2.9; 95% CI, 1.15-7.24). CONCLUSION: The risk for MS, T2DM, hyperglycemia, and dyslipidemia is related to the carriage of the T allele of the G276Т polymorphism in the ADIPOQ gene in ethnic Kyrgyz women.

[Association Between T455C Polymorphism of Apolipoprotein C-III Gene, Insulin Resistance and Metabolic Syndrome Components].

AIM: to study an association between T455C apolipoprotein C-III (apo C-III) gene polymorphism, insulin resistance (IR), metabolic syndrome (MS) and its components in a Kyrgyz ethnic group. MATERIAL AND METHODS: 259 persons: 162 patients with MS and 97 sex and age matched controls without MS, diabetes mellitus and cardiovascular diseases were included in the study. Clinical examination with arterial blood pressure, anthropometric data measurement and laboratory tests for blood glucose and lipid parameters were performed in all included persons. In 140 patients test for immunoreactive serum insulin was done. DNA was extracted from blood cells and T455C polymorphism.

[The association of leptin with dislipidemia in group of ethnic Kirghiz].

The article deals with results of evaluation of relationship between leptin and lipid indicators in group of ethnic Kirghiz. The sampling included 322 ethnic Kirghiz (145 males and 177 females) aged from 30 to 75 years. To all patients was applied general clinical examination, anthropometric examination (height, body mass, waist circumference, thighs circumference). The body mass index was calculated. The level of glucose (on an empty stomach), lipids spectrum and leptin of blood serum were measured. The average age of patients consisted 57.7 +/- 9.6 years and average level of leptin was 7.8 ng/ml. The patients were allocated to three groups depending of tertile of leptin (< 3; 3.0-5.51; > or = 5.52 ng/ml in males; 9.6; 9.6-16.6; > or = 16.7 ng/ml in females). In patients from upper tertile as compared with patients from lower tertiles are noted high values of triglycerides (p < 0.001), total cholesterol (p < 0.O01), in males and triglycerides (p = 0.02) in females. Leptin correlated with body mass index (in males: r = 0.68, p < 0.01; in females: r = 0.74, p < 0.001), concentration of triglycerides (in males: r = 0.301, p < 0.001; in females: r = 0.194, p < 0.001). Leptin correlated with total cholesterol in males (r = 0.214, p < 0.05) and with cholesterol of lipoproteins of high density in females (r = 0.156, p < 0.05). The level of leptin in group of ethnic Kirghiz is associated with dislipidemia, obesity, including abdominal obesity.

[Association of leptin with obesity and hypertension in an ethnic Kyrgyz group].

AIM: To study an association of the level of leptin, obesity, and hypertension in a group of ethnic Kyrgyz. SUBJECTS AND METHODS: Three hundred and twenty-two Kyrgyz people (145 men and 177 women) who were aged above 30 years and resided in the Kyrgyz Republic were examined. They underwent physical examination involving the collection of complaints and medical history data, objective examination, and anthropometric (height, weight, waist and hip circumference (WC and HC), body mass index (BMI)) and blood pressure (BP) measurements. The persons filled out the Finnish Diabetes Risk Assessment Form including data on vegetable consumption (daily or every other day) and exercise (more or less than 30 min per day). Fasting plasma glucose and serum leptin levels were determined. RESULTS: All the study participants were allocated to 4 groups according the quartile of leptin levels: < 2.2, 2.2-4.2, 4.3-6.34, and > 6.34 ng/ml for men and < 8.05, 8.05-13.4; 13.5-19.09, and > 19.09 ng/ml for women. The persons in the highest leptin quartile were found to have higher BMI, WC, systolic and diastolic BP (SBP and DBP), and blood glucose levels than those in the lowest quartile. Elevated leptin levels were associated with the higher risk of hypertension. Leptin levels correlated with BMI (r = 0.719; p < 0.001 for men and r = 0.74; p < 0.001 for women) and WC (r = 0.684; p < 0.001 for men; and r = 0.649; p < 0.001 for women). There was also a correlation of leptin levels with SBP (r = 0.355; p < 0.001 and r = 0.277; p < 0.001) and DBP (r = 0.426; p < 0.001 and r = 0.228; p < 0.01) in men and women, respectively. CONCLUSION: Leptin levels were associated with obesity and hypertension in the group of ethnic Kyrgyz people.

[An association of the 825 polymorphism of the g protein 3 subunit with obesity in Kyrgyz population].

GOAL: To study an association of G protein (GP) 3 subunit 825 polymorphism with obesity in native Kyrgyzes. MATERIAL AND METHODS: 210 persons: 89 patients (female - 35, male - 54) with obesity (body mass index [BMI] more or equal 30 kg/m2) and 121 apparently healthy controls (38 female, 83 male) with normal BMI. Arterial blood pressure, anthropometric measurement and laboratory tests for blood glucose and lipid parameters were performed in all examined persons. DNA was extracted from blood cells and GP3 subunit 825 polymorphism was determined by PCR method. RESULTS: groups with TT and CT genotypes were combined together because of the rare frequency of TT genotype. Prevalence of + genotypes in group with obesity (0.72) was significantly higher than in controls - 0.52 (odds ratio 2.55, 95% confidence interval [CI] 1.31-4.23; =0.004). Arterial hypertension (45 vs. 31.3%; =0,049) and obesity (51.2 vs. 30%; p<0.01) occurred more often in + genotypes carriers compared with CC homozygotes. A logistic regression model for obesity showed significant effect of 825T allele (relative risk [RR] 2.89, 95% CI 1.25-6.7; =0.013) and irregular intake of vegetables (RR 3.47, 95% CI 1.52-7.94; =0.003) as predictors of obesity development independent of age, sex and physical activity level. In the regression model for arterial hypertension the 825T allele lost its significance after adjustment for obesity. CONCLUSION: GP3 subunit 825 allele in native Kyrgyzes is associated with obesity.

[Renal anemia and cardiac remodeling in patients with chronic glomerulonephritis].

AIM: To study the pattern of cardiac remodeling and its association with anemia in patients with chronic glomerulonephritis (CGN). SUBJECTS AND METHODS: Sixty patients aged 21 to 58 years (mean age 38.1+9.8 years) with the hypertensive form of CGN were examined. According to the presence of anemia, the patients were divided into 2 groups with 30 persons in each. All the patients underwent physical examination with verification of the diagnosis, estimation of the volume of red blood cells, and echocardiography. RESULTS: The patients with anemia as compared to those with CGN and without anemia were found to have a statistically significant increase in the left atrial size (3.6 +/- 0.6 cm versus 3.3 +/- 0.3 cm; p < 0.05), left ventricular (LV) end-diastolic size (5.4 +/- 0.6 cm versus 5.1 +/- 0.4 cm; p < 0.05), LV end-systolic size (3.7 +/- 0.7 cm versus 3.3 +/- 0.5 cm; p < 0.05), and LV mass index (141.8 +/- 60.5 g/m2 versus 113.5 +/- 30.8 g/m2; p < 0.05). Correlation analysis revealed statistically significant correlations between red blood cell levels, LV end-systolic and end-diastolic sizes and ejection fraction (EF) in the anemia group while this correlation was absent in the non-anemia group. Group 1 showed a correlation between blood pressure (BP) (mainly diastolic BP), LV sizes and wall thickness. CONCLUSION: The patients with chronic glomerulonephritis complicated with anemia exhibited LV remodeling as LV dilatation.

[Association of C677T gene polymorphism of methylenetetrahydrofolate reductase with insulin resistance among Kirghizes].

AIM: To study an association of C677T gene polymorphism of methylenetetrahydrofolate reductase (MTHFR) and insulin resistance (IR) among ethical Kirghizes. METHODS: 132 Kirghiz patients with IR according to HOMA index (n=132) and sex and age matched patients without IR, diabetes mellitus (DM) type 2 or metabolic syndrome (MS) (n=132) were included into this study. Measurements of blood pressure (BP), body mass index, waist and hip circumference, fasting blood sugar, insulin, lipid parameters and C677T gene polymorphism of MTHFR were performed in all patients. RESULTS: Frequency of CT and TT genotypes was significantly higher in patients with IR than in controls (2 - 7.22, p - 0,027, OR - 1.68, 95% confidence interval 1.13-2.5, p=0.027). T677 allele was also associated with obesity, hypertriglyceridemia and low level of high density lipoprotein cholesterol (HDL-C). CONCLUSION: In Kirghizes carriage of T677 allele of MTHFR gene was associated with IR, abdominal obesity, hypertriglyceridemia and low HDL-C level.

[Association of the serum level of apolipoprotein E with coronary artery disease and carotid artery atherosclerosis in Kyrgyz men with dyslipidemia].

AIM: To study an association of the serum level of apolipoprotein E (apo-E) with risk factors for coronary heart disease (CHD), blood lipids and that with CHD and carotid artery (CA) atherosclerotic lesion in Kyrgyz men with dyslipidemia. SUBJECTS AND METHODS: One hundred and three Kyrgyz men, including 48 with CHD and 55 without this disease, were examined. A clinical examination was performed and blood lipid composition and serum glucose and apo-E levels were determined. The diagnosis of CHD was established in accordance with the conventional criteria. Whether atherosclerosis was present was determined by ultrasound duplex scanning. RESULTS: Low serum apo-E concentrations were associated with the presence of obesity, the higher blood levels of glucose and triglycerides. There was no correlation with other lipid metabolic parameters and the presence of CHD. A nonlinear relationship was noted between serum apo-E levels and CA atherosclerotic lesion, which was more frequently observed in patients with the apo-E level in the lower and upper quartiles. CONCLUSION: Low serum apo-E content is a poor factor and associated with obesity, hypertriglyceridemia, elevated serum glucose levels, and the development of CA atherosclerosis.

[Ethnic differences in apolipoprotein B levels in hyperlipidemia in Russian and Kirghiz populations]. / Etnicheskie osobennosti v urovne apolipoproteina B pri giperlipidemiiakh u russkikh i kirgizov.

AIM: To evaluate the levels of apolipoprotein B (apo-B) and coronary heart disease (CHD) risk factors in Russians and the Kirghiz with primary hyperlipidemia (PHL). MATERIAL AND METHODS: Lipid spectrum of the blood (LDLP and HDLP cholesterol, total cholesterol, triglycerides), apo-B, CHD risk factors were studied in 60 Russian and 75 Kirghis patients with PHL aged 28 to 67 years (mean age 50.0 +/- 7.59 years, 56 females and 79 males). RESULTS: In Russians a mean level of LDLP cholesterol and apo-B was significantly higher than in Kirghiz patients (3.95 +/- 1.29 mmol/l vs 3.51 +/- 1.17 mmol/l, p = 0.042; 173.3 +/- 57.3 mg/dl vs 145.5 +/- 49.3 mg/dl, p = 0.003, respectively). CHD in both ethnic groups occurred with similar rates. The multifactorial regression analysis shows that an apo-B concentration can serve an independent risk factor associated with CHD in the Kirghiz population (beta = 0.25, p = 0.03) while in Russians living in Kirghizia this factor is a low content of HDLP cholesterol (beta = -0.25, p = 0.05).