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At present, little is known about the genetic background of breast cancer (BC) in Kyrgyz. Therefore, the aim of this study was to assess gene-to-gene interactions and the contribution of p.Arg72Pro (TP53 gene), p.Gln399Arg (XRCC1 gene), p.Arg194Trp (XRCC1 gene), g.4682G > A (TNFα gene), p.Val353Ala (HMMR gene), c.14 + 309 T > G (MDM2 gene) and g.38444 T > G (PALB2 gene) polymorphic loci in breast cancer (BC) risk in females of Kyrgyz ethnicity. The case–control study comprised 103 females with histologically verified BC and 102 controls with no cancer. We used polymerase chain reaction-based restriction fragment length polymorphism to genotype polymorphic loci. Gln/Arg heterozygous variant of XRCC1 gene’s p.Gln399Arg locus, as well as combined carriage of Arg/Gln//Arg/Pro of XRCC1/TP53; Arg/Gln//T/T of XRCC1/MDM2; Arg/Gln//G/G and Arg/Gln//G/A of XRCC1/TNFα, Arg/Gln//T/T of XRCC1/PALB2; Arg/Gln//Arg/Arg and Arg/Gln//Arg/Trp for p.Gln399Arg and p.Arg194Trp polymorphic loci of XRCC1 were associated with BC in Kyrgyz females. TP53, XRCC1, TNFα, HMMR, MDM2 and PALB2 genes’ polymorphic site combinations appear to be candidate markers of genetic predisposition to BC in Kyrgyz population and prompt targeted personalized care.

Molecular studies on donkey mitochondrial sequences have clearly defined two distinct maternal lineages involved in domestication. However, domestication histories of these two lineages remain enigmatic. We therefore compared several population characteristics between these two lineages based on global sampling, which included 171 sequences obtained in this study (including Middle Asian, East Asian, and African samples) plus 536 published sequences (including European, Asian, and African samples). The two lineages were clearly separated from each other based on whole mitochondrial genomes and partial non-coding displacement loop (D-loop) sequences, respectively. The Clade I lineage experienced an increase in population size more than 8 000 years ago and shows a complex haplotype network. In contrast, the population size of the Clade II lineage has remained relatively constant, with a simpler haplotype network. Although the distribution of the two lineages was almost equal across the Eurasian mainland, they still presented discernible but complex geographic bias in most parts of Africa, which are known as their domestication sites. Donkeys from sub-Saharan Africa tended to descend from the Clade I lineage, whereas the Clade II lineage was dominant along the East and North coasts of Africa. Furthermore, the migration routes inferred from diversity decay suggested different expansion across China between the two lineages. Altogether, these differences indicated non-simultaneous domestication of the two lineages, which was possibly influenced by the response of pastoralists to the desertification of the Sahara and by the social expansion and trade of ancient humans in Northeast Africa, respectively.

Background: The aim of this study was to ascertain the magnitude of association of gene ТР53 Arg72Pro polymorphic marker with cervical cancer (CC) in Kyrgyz women. Methods: We identified and included 205 women of Kyrgyz ethnicity for this case-control study, of whom N=103 were women (mean age 53.5 ± 10.0 years) with histologically confirmed CC and N=102 controls (mean age 46.5 ± 8.5 years). We detected human papilloma virus (HPV) DNA types 16 and 18 using polymerase chain reaction (PCR) with hybridization/fluorescent detection. Genotypes of ТР53 gene Arg72Pro polymorphism were identified using PCR-RFLP assay. Results: Eighty-eight percent (90/103) women with CC had HPV, of whom 43.4% (39/90) had HPV type 16, 24.4% (22/90) had HPV type 18, whereas 32.2% (29/90) carried both types. The univariate analysis of allele and genotype distribution of Arg72Pro polymorphic marker of ТР53 gene showed no difference between CC and control groups (χ2=1.24, р=0.54). However, when CC cases associated with HPV were tested against controls, Arg72 allele and Arg72Arg genotype prevalence were greater compared to controls (χ²=7.25; р=0.027 for genotypes and χ²=6.83; р=0.009 for alleles). In HPV-positive women, Arg72Arg genotype of ТР53 gene was associated with a 1.85-fold increase in the likelihood of CC (OR=1.85 [95% confidence interval (CI) 1.03-3.32]), whereas Arg72 allele increased this likelihood 1.94-fold (OR=1.94 [95% CI 1.20-3.15]). Conclusions: Arg72Arg genotype and Arg72 allele of ТР53 gene in Kyrgyz women increase the risk of HPV-associated CC.

This abstract was not presented at the conference. Citation Format: Semetei Kyzy A, Makimbetov E, Kudaibergenova I, Isakova J. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-10-05.

The aim of this study was to ascertain the polymorphic markers profile of ADIPOQ,KCNJ11 and TCF7L2 genes in Kyrgyz population and to analyze the association of polymorphic markers and combinations of ADIPOQ gene's G276T locus, KCNJ11 gene's Glu23Lys locus and TCF7L2 gene's VS3C>T locus with type two diabetes (T2D) in Kyrgyz population. In this case‐control study, 114 T2D patients 109 non‐diabetic participants were genotyped using polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP). Two individual polymorphisms (ADIPOQ rs1501299, KCNJ11 rs5219) were found to be associated with T2D. We found two (Lys23Lys/CC and Glu23Lys/CT) of the overall nine combinations, which were more prevalent in T2D group compared to controls (χ2 = 4.21, P = 0.04). Lys23Lys/CC combination was associated with a 2.65‐fold increased likelihood of T2D (OR = 2.65, 95% CI 1.12‐6.28), whereas the Glu23Lys/CT combination also increased such likelihood (OR = 3.88, 95% CI 1.27‐11.91). This study demonstrated some association of 276T allele and ADIPOQ gene G276T heterozygous genotype as well as KCNJ11 gene 23Lys allele with T2D in ethnic Kyrgyz, but study results should be interpreted with caution because of the limited statistical power.

Aim — in this study, we investigated whether polymorphisms Glu23Lys in KCNJ11 are associated with Type 2 diabetes mellitus (T2DM) in the Kyrgyz population. Material and methods . We genotyped 287 Kyrgyz individuals. A case—control study was performed, including 178 patients with T2DM (female — 55, male — 123, average age 54±6,6) and 109 non-diabetes controls (female — 48, male — 61, average age 50±8,4). The genotypes of polymorphic position Glu23Lys of KCNJ11 were determined by PCR-RFLP assay. Results . Genotypes Glu23Lys and Lys23Lys, containing the minor allele 23Lys, were more frequent in the group of type 2 diabetes (χ 2 =4,09; p =0,043). The allele 23Lys of KCNJ11 gene is associated with a high risk of developing type 2 diabetes in the Kyrgyz population [OR=1,46 (1,02—2,07); p =0,036]. Homozygous genotype Glu23Glu and allele Glu23 reduces the risk of developing type 2 diabetes [OR=0,61 (0,37—0,99); p =0,043 and OR=0,69 (0,48—0,98); p =0,037], respectively). Conclusion . Polymorphisms Glu23Lys of KCNJ11 gene are associated with the risk of Type 2 diabetes mellitus in the Kyrgyz Population according to the dominant and additive models of inheritance of the trait. Our results indicate that the allele 23Lys of KCNJ11 gene confers an elevated risk for the development of Type 2 diabetes mellitus in the Kyrgyz population.

Background The aim of this study was to identify mutations of rpoB, katG, inhA and ahp-genes associated Mycobacterium tuberculosis resistance to rifampicin (RIF) and isoniazid (INH) in Kyrgyz Republic. We studied 633 smear samples from the primary pulmonary tuberculosis (TB) patients. We verified Mycobacterium tuberculosis susceptibility to RIF and INH using culture method of absolute concentrations, and commercially available test named “TB-BIOCHIP” (Biochip-IMB, Moscow, Russian Federation). Results For RIF-resistance, TB-BIOCHIP’s sensitivity and specificity were 88% and 97%, 84% and 95% for INH-resistance, and 90% and 97% for multi-drug resistance (MDR). In RIF-resistant strains, TB-BIOCHIP showed mutations in codons 531 (64.8%), 526 (17.3%), 516 (8.1%), 511 (5.4%), 533 (3.2%), 522 (0.6%) and 513 (0.6%) of rpoB gene. The most prevalent was Ser531 > Leu mutation (63.7%). 91.2% of mutations entailing resistance to INH were in katG gene, 7% in inhA gene, and 1.8% in ahpC gene. Ser315→Thr (88.6%) was the most prevalent mutation leading to resistance to INH. Conclusions In Kyrgyz Republic, the most prevalent mutation in RIF-resistant strains was Ser531 → Leu in rpoB gene, as opposed to Ser315 → Thr in katG gene in INH-resistant Mycobacterium tuberculosis. In Kyrgyz Republic, the major reservoir of MDR Mycobacterium tuberculosis were strains with combined mutations Ser531 → Leu in rpoB gene and Ser315 → Thr in katG gene. TB-BIOCHIP has shown moderate sensitivity with the advantage of obtaining results in only two days.

Background The aim of this study was to quantify the association of Val109Asp polymorphism of intelectin 1 (ITLN1) gene with the abdominal obesity (AO) in Kyrgyz population. Methods Patients admitted to annual screening at a local outpatient facility were enrolled or this study. We genotyped 297 nonrelated adults of Kyrgyz ethnicity, of whom 127 were AO patients, including 46 men and 81 women with the mean age 53.2 ± 7.1 years, and 170 non-obese controls, including 61 men and 109 women with the mean age 52.0 ± 9.0 years. AO was defined as having waist circumferences ≥ 102 cm in men and ≥ 88 cm in women. We used PCR-RFLP method to define Val109Asp polymorphism of ITLN1 gene. Results Asp109Asp, Asp109Val and Val109Val genotypes were found in 48%, 40%, and 12% of AO patients respectively, and in 53%, 43%, and 4% of controls, whereas Val109Val homozygous genotype of ITLN1 gene Val109Asp polymorphic marker was significantly more prevalent in AO patients. In Kyrgyz population, Val109Val genotype of ITLN1 gene increased the risk of AO (odds ratio (OR) 3.12, 95% CI 1.23–7.90). Asp109Asp homozygous genotype, on opposite, was not associated with this condition (OR 0.82, 95% CI 0.53–1.30). Finally, the allelic variants of Val109Asp polymorphism of ITLN1 gene were not associated with AO. Conclusion Significant increase in the frequency of Val109Val genotype of ITLN1 gene in AO patients may be indicative of some potential role of ITLN1 gene in molding genetic predisposition to AO in the Kyrgyz. This requires further elaboration in the future studies.

summary Kyrgyzstan is a post-Soviet country in Central Asia marked with high incidence and mortality rates of tuberculosis (TB). The present study provided first assessment of Mycobacterium tuberculosis population structure and drug-resistance in civilian population here. The collection included 103 M. tuberculosis DNA samples subjected to the analysis of rifampin and isoniazid resistance mutations and spoligotyping. The major spoligotype-defined families were Beijing (n ¼ 62), T (n ¼ 14), LAM (n ¼ 9), Ural-2 (n ¼ 6) and Ural1( n ¼ 3). Genotypically, 20 isolates were RIF-resistant, 28 were INH-resistant, 17 were multidrugresistant. Drug resistant isolates were more prevalent among Beijing than non-Beijing groups (P ¼ 0.03). The predominance of the mainly “Russian” spoligotypes among the non-Beijing strains (LAMRUS and Ural-1) in this study along with previously demonstrated prevalence of the Russia-specific subtype of the Beijing family in Kyrgyz prison (Mokrousov et al., 2009) suggest that the current population structure of M. tuberculosis in Kyrgyzstan has been mainly formed within the course of the 20th century when the country was a part of the Russian Empire and Soviet Union. On the other hand, a prevalence of the Asia-specific Ural-2 type in the oldest age group (68e85 years old; P < 0.0001) may present a heritage of the more distant historical events. In summary, we suggest: (i) a clear shift of the local M. tuberculosis population structure during the last 100 years and (ii) a critical impact of the Beijing genotype on the current situation with drug resistant TB in Kyrgyzstan.

High-coverage whole-genome sequence studies have so far focused on a limited number1 of geographically restricted populations2, 3, 4, 5, or been targeted at specific diseases, such as cancer6. Nevertheless, the availability of high- resolution genomic data has led to the development of new methodologies for inferring population history7, 8, 9 and refuelled the debate on the mutation rate in humans10. Here we present the Estonian Biocentre Human Genome Diversity Panel (EGDP), a dataset of 483 high-coverage human genomes from 148 populations worldwide, including 379 new genomes from 125 populations, which we group into diversity and selection sets. We analyse this dataset to refine estimates of continent-wide patterns of heterozygosity, long- and short-distance gene flow, archaic admixture, and changes in effective population size through time as well as for signals of positive or balancing selection. We find a genetic signature in present-day Papuans that suggests that at least 2% of their genome originates from an early and largely extinct expansion of anatomically modern humans (AMHs) out of Africa. Together with evidence from the western Asian fossil record11, and admixture between AMHs and Neanderthals predating the main Eurasian expansion12, our results contribute to the mounting evidence for the presence of AMHs out of Africa earlier than 75, 000 years ago.

This case–control study evaluates a possible association between high altitude pulmonary hypertension (HAPH) and sleep apnoea in people living at high altitude.Ninety highlanders living at altitudes >2500 m without excessive erythrocytosis and with normal spirometry were studied at 3250 m (Aksay, Kyrgyzstan); 34 healthy lowlanders living below 800 m were studied at 760 m (Bishkek, Kyrgyzstan). Echocardiography, polysomnography and other outcomes were assessed. Thirty-six highlanders with elevated mean pulmonary artery pressure (mPAP) >30 mmHg (31–42 mmHg by echocardiography) were designated as HAPH+. Their data were compared to that of 54 healthy highlanders (HH, mPAP 13–28 mmHg) and 34 healthy lowlanders (LL, mPAP 8–24 mmHg).The HAPH+ group (median age 52 years (interquartile range 47–59) had a higher apnoea–hypopnoea index (AHI) of 33.8 events·h−1(26.9–54.6) and spent a greater percentage of the night-time with an oxygen saturation −1(3.6–16), T−1(1.4–12.6), Tversusothers. In highlanders, multivariable regression analysis confirmed an independent association between mPAP and both AHI and TPulmonary hypertension in highlanders is associated with sleep apnoea and hypoxaemia even when adjusted for age, gender and body mass index, suggesting pathophysiologic interactions between pulmonary haemodynamics and sleep apnoea.

To study the association of adiponectin gene G276Т (ADIPOQ) polymorphism with the development of metabolic syndrome (MS) in ethnic Kyrgyz patients.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.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 (p0.05), glucose (p0.05), 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).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.Цель исследования. Изучить ассоциацию полиморфного маркера G276Т гена адипонектина с развитием метаболического синдрома (МС) у пациентов киргизской национальности. Материалы и методы. Обследовали 171 пациента с МС и 117 лиц без МС (группа сравнения). МС констатировали на основании модифицированных критериев АТР III. Генотипы полиморфизма G276T гена адипонектина (ADIPOQ) определяли методом полимеразной цепной реакции с анализом полиморфизма длин рестрикционных фрагментов. Результаты. При разделении группы больных МС и контрольной группы по половому признаку статистически значимые различия по распространенности аллелей и генотипов выявлены только среди женщин. Наблюдалась более высокая распространенность генотипов GT+ТТ (53% против 34%; χ2=5,942; р=0,014) и аллеля Т (30% против 19%; χ2=4,489; р=0,0341) в подгруппе больных МС женщин по сравнению с женщинами из контрольной группы. У женщин киргизской национальности аллель Т полиморфного локуса G276Т гена ADIPOQ ассоциирован с развитием МС (отношение шансов - ОШ 1,82 при 95% доверительном интервале - ДИ от 1,04 до 3,19), сахарного диабета 2-го типа - СД-2 (ОШ 2,63 при 95% ДИ от 1,05 до 6,56), с высокими уровнями лептина (p0,05), глюкозы (р0,05), триглицеридов (ОШ 3,06 при 95% ДИ от 1,05 до 8,93), холестерина липопротеидов низкой плотности (ОШ 2,80 при 95% ДИ от 1,07 до 7,31) и сниженным уровнем холестерина липопротеидов высокой плотности (ОШ 2,9 при 95% ДИ от 1,15 до 7,24). Заключение. Риск развития МС, СД-2, гипергликемии и дислипидемии у женщин киргизской национальности связан с носительством аллеля Т полиморфного маркера G276T гена ADIPOQ.

Tibetans have been living at altitudes over 3500 m for ~20,000 years and have developed unique beneficial evolutionary genetic adaptions (PMID:28448578). Our previous study identified selected genetic haplotypes in two genes, EPAS1 (encoding hypoxia-inducible factor 2-alpha [HIF2-a], a transcription factor that mediates the hypoxic response), and EGLN1 (encoding prolyl hydroxylase 2 [PHD2], a principal negative regulator of HIF stability (PMID:25129147). The presence of these two haplotypes correlates with lower hemoglobin levels in Tibetans compared to other highlanders. However, the entire diverse complex of molecular mechanisms of high altitude adaptation is still largely unknown and our study showed that neither EPAS1 nor EGLN1 variants fully explain the mechanism of protection from polycythemia in Tibetans in high altitude (PMID:28233034). We found an enriched haplotype in the PKLR gene (encoding pyruvate kinase [PK] expressed only in liver and red blood cells). The PK enzyme is in the terminal portion of the glycolytic pathway, and its decreased activity leads to accumulation of proximal glycolytic intermediates, including 2,3-diphosphoglycerate (DPG) which shifts the hemoglobin dissociation curve to right (high p50) and increases oxygen release to tissues from a unit of hemoglobin. We hypothesized that Tibetan enriched PKLR variants might improve oxygen delivery to tissues and help explain the protection from polycythemia at high altitude. Genomic analyses revealed that this PKLR haplotype is enriched in Tibetans but is not unique to Tibetans. It has the highest frequency in Tibetans (89%), with a lower prevalence in Chinese and Mongolians (~77%), Kyrgyz (~60 %), Aymara (~44 %), and Colombians (~30 %) and a much lower frequency in Caucasians (11%), perhaps explaining the heterogeneity of responses to hypoxia within and among these populations. Our study of reticulocyte RNA showed that transcript levels of PKLR progressively decrease with increasing altitude in controls and even more in Tibetans with the Tibetan evolutionary selected PKLR haplotype. Tibetans with the PKLR haplotype (heterozygotes and homozygotes) have lower PKLR transcript levels than wild type Tibetans. Because of the paucity of wildtype PKLR haplotype in Tibetans and the challenges of acquiring Tibetan samples in high altitude in China, we collected samples from 125 m (Cheboksary, Chuvashia); 800 m (Bishkek, Kyrgyzstan) and 2640 m (Bogota, Colombia). PK activity, PKLR transcript levels, and ATP decreased at 2640 m compared to 800 m, while p50 increased at 2640 m. PKLR transcript levels correlated with PK activity and ATP and inversely correlated with p50. PK activities also correlated with PKLR transcript levels and ATP and inversely correlated with p50. At 2640 m, PK activity was lower and p50 levels were higher in those with the enriched PKLR haplotype. These results demonstrate that increasing altitude decreases PK activity, resulting in increasing p50 providing a molecular basis for the previously reported improvement of oxygen delivery at high altitude (PMID:17394415). To study the roles of HIFs in the regulation of PKLR gene expression, we also collected samples from Chuvash polycythemia (CP) homozygotes and Chuvash controls. CP homozygotes have a mutation in the VHL gene, a negative regulator of HIFs, that results in augmented HIF levels. CP homozygotes had lower PKLR mRNA in reticulocytes, PK activity, and PKR protein levels in red blood cells compared to controls, while their 2,3 DPG levels were higher. These data confirm that PKLR expression levels are negatively regulated by HIFs. Our findings demonstrate that individuals in high altitudes have lower PKLR transcript levels and PK activity, resulting in high 2,3DPG and p50 which shifts the hemoglobin dissociation curve to right. This decreases affinity of hemoglobin for oxygen, which improves tissue oxygen delivery and as such is another mechanism in Tibetans that protects from high altitude polycythemia. We also demonstrate that HIFs negatively regulate PKLR expression, leading to better oxygen release from hemoglobin at high altitude. Disclosures Kosinski: Agios: Employment, Equity Ownership. Kung:Agios: Employment, Equity Ownership. van Wijk:RR Mechatronics: Research Funding; Agios Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Hypoxia-induced and high altitude pulmonary hypertension are a major problem in the mountain areas of the world. The asymmetric methylarginines (ADMA) inhibit nitric oxide (NO) synthesis by competing with L-arginine, and high levels of plasma ADMA predict adverse outcomes in pulmonary hypertension. However, little is known about the regulation of the ADMA-NO pathway in animals adapted to high altitudes. We measured the plasma ADMA concentration, endothelial NO synthase (eNOS), dimethylarginine dimethylaminohydrolases (DDAH) protein expression, and DDAH activities in the lungs from yaks. Although the yaks are hypoxemic, cardiac function and pulmonary arterial pressures are almost normal, and we found decreased DDAH expression and activity in association with reduced plasma ADMA concentrations. The eNOS expression was significantly higher in yaks. These results indicate that augmented endogenous NO activity in yaks through the ADMA-DDAH pathway and eNOS upregulation account for the low pulmonary vascular tone observed in high altitude adapted yaks.

It is commonly thought that human genetic diversity in non-African populations was primarily shaped by a recent out-of-Africa dispersal. Here we present a large geographical Y chromosome study using 459 high coverage sequences, including 302 newly reported here. We date the Y chromosomal Most Recent Common Ancestor (MRCA) in Africa at 254 (95% CI 192- 307) kya and differentiation of African and non-African lineages 52-121 kya. The age estimates for major non-African founder haplogroups cluster closely in a narrow time interval at 47-52 kya, consistent with a rapid initial colonization model of Eurasia and Oceania after the out-of-Africa bottleneck. We find that the highest basal Y chromosome diversity outside Africa has been preserved in South and Southeast Asians while extant Y chromosome diversity in Europe and the Near East stems from a small number of mid-Holocene founders. In contrast to demographic reconstructions based on mtDNA, we infer a second strong bottleneck, followed by a fast recovery in Old World populations dating to the last 10 ky. We hypothesize that this bottleneck is caused by cultural changes affecting variance of reproductive success among males.

Endothelin-1 (ET-1) plays a critical role in the regulation of pulmonary vascular tone. The aim of this study was to investigate the role of ET-1 in the pathogenesis of high altitude pulmonary arterial hypertension (HAPH).Pulmonary artery pressure (PAP) was measured by echocardiography in permanent residents of the Kyrgyz Republic (3200-4000 m above sea level) both before and 3 h after a single oral dose of ET receptor antagonist, bosentan (125 mg). Plasma ET-1 levels were measured by ELISA assay. Genomic DNA was extracted from peripheral blood samples and the frequency of -3a and -4a alleles of the ET-1 gene determined by PCR.Plasma ET-1 in HAPH highlanders was significantly higher than in healthy subjects (7.05±2.35 vs. 4.65±1.65 pg/ml, p0.002). After the treatment with 125 mg bosentan, systolic PAP decreased from 46±1.9 to 37±2.2 mm Hg (p0.01), and pulmonary artery acceleration time (PAAT) increased from 0.086±0.001 to 0.098±0.001 sec (p0.001). The frequency of the -4a allele was significantly higher in HAPH patients compared to healthy highlanders (0.43 vs. 0.3, χ(2)=4.3, p=0.03).Increased ET-1 levels play an important role in development of HAPH.

Here, we present results of the first study of the Mycobacterium tuberculosis genotypes circulating in Kyrgyzstan. We focused on the incarcerated population known to be at high-risk for tuberculosis (TB) and with a significant impact on TB incidence in the general population. Beijing genotype was detected in 42 of 56 M. tuberculosis sputum-extracted DNA samples from newly-diagnosed adult pulmonary TB patients. RIF and INH resistance was genotypically detected in 28% and 55% samples; 13 of 15 MDR strains belonged to Beijing genotype. 12-locus MIRU-VNTR typing showed 8 of 56 samples to be mixed cases; 7 of them contained a Beijing strain. MIRU analysis demonstrated a high homogeneity of the studied collection (HGI = 0.66) while 28 of 56 strains had a profile 223325153533 corresponding to Beijing/M2 subtype highly prevalent in different Russian settings. Three hypervariable loci, QUB-3232, VNTR-3820 and VNTR-4120, permitted to further subdivide 28 Beijing/M2 strains into 11 subtypes shared by 1 to 9 strains. To conclude, all markers taken together, the penitentiary population of M. tuberculosis in Kyrgyzstan exhibited a strong genetic affinity to Russia and a weak relatedness to East Asia.