ANALYSIS OF SOCIAL AND DEMOGRAPHIC AND CLINICAL CHARACTERISTICS OF PATIENTS WITH PARANOID SCHIZOPHRENIA OF THE KAZAKH ETHNIC GROUP IN THE REPUBLIC OF KAZAKHSTAN.

The socio-demographic and clinical characteristics of patients of the Kazakh ethnic group suffering from paranoid schizophrenia were studied in order to increase the efficiency of providing them with specialized psychiatric care in the Republic of Kazakhstan. The analysis of social and demographic characteristics of the examined group of 1200 patients of the Kazakh population with a clinically verified diagnosis: "Paranoid schizophrenia" (F20.0) in the period from 2021 to 2023 showed that these were mainly people of average working age (31-50 years - 55.59%), a significant part of whom, despite a fairly good level of education, were socially maladapted in family and household terms, more than 80% of them had a disability due to mental illness, which it may indicate the severity of the underlying mental disorder. The analysis of clinical characteristics (according to the PANSS scale) showed that in patients with a continuous type of paranoid schizophrenia, the severity of mental disorders (93.06 points) significantly exceeded the same indicator in patients with an episodic type of the disease (76.87 points), mainly due to the difference in the scale of general psychopathological symptoms. It is established that for people of the Kazakh ethnic group suffering from paranoid schizophrenia, concomitant narcological pathology is not characteristic.

Distribution of HLA-A, -C, -B, -DRB1, and -DQB1 polymorphisms in the Korean minority in Kazakhstan, and relatedness to neighboring and distant populations.

BACKGROUND: Among the 125 ethnicities and linguistic groups in Kazakhstan, Koreans represent the eighth minority numerically. HLA class I and class II allele frequencies and extended haplotypes were studied for the first time and were compared to related and distant populations worldwide. METHODS: HLA class I (A, B, C) and class II (DRB1, DQB1) profile was investigated in Kazakhstani Koreans, and were compared to other populations using standard genetic distances (SGD), neighbor-joining dendrograms, correspondence, and haplotype analysis. RESULTS: One hundred and thirty-one HLA alleles were identified in Koreans living in Kazakhstan, with A*02:01 (23.08%), B*35:01 (8.24%), C*01:02 (15.38%), DRB1*08:03 (9.89%), and DQB1*03:01 (21.98%) being the most frequent alleles. A*03:01 âˆ¼ B*07:02 (3.85%), B*08:01 âˆ¼ DRB1*03:01 (3.85%), B*07:02 âˆ¼ C*07:02 (7.14%), and DRB1*08:03 âˆ¼ DQB1*06:01 (9.34%) were the most frequent two-locus haplotypes, while A*02:01 âˆ¼ B*18:01 âˆ¼ C*07:01 âˆ¼ DRB1*11:04 âˆ¼ DQB1*03:01 and A*33:03 âˆ¼ B*44:03 âˆ¼ C*14:03 âˆ¼ DRB1*13:02 âˆ¼ DQB1*06:04 (2.2% each) were the most frequent five-locus haplotypes. CONCLUSION: Korean minority in Kazakhstan was closely related to East Asians, including Mongolians (SGD, 0.044), Tuvans (East Siberia; SGD, 0.081), Burayts (Siberia; SGD, 0.094), but distant from East Mediterranean such as Lebanese (SGD, 0.367), Greek (SGD, 0.377), and Saudi (SGD, 0.414), and most Siberians (SGD, 0.473-0.699). This relatedness could be mainly attributed to massive migration of Koryo Saram to Kazakhstan in the 20th century.

Elemental composition of hair as a marker for forensic human identification.

BACKGROUND: Hair is one of the most common evidence types found in criminal investigations. Analysis of human hair reveals the mineral composition accumulated within it over time spent in a specific area, thereby providing additional information for forensic identification. MATERIALS AND METHODS: To identify patterns of the elemental composition of hair in territories with different natural and anthropogenic features, hair samples of 1238 residents and 217 corpses of Central Kazakhstan were studied. The determination of 14 chemical elements in hair by inductively coupled plasma atomic emission spectrometry were presented. The data were analysed in terms of place of residence, gender, age and condition. RESULTS: The results showed that the concentration of trace elements like Cu, Fe, Cd, and As significantly differed among all regions (p < 0.05). The composition of hair samples obtained from women significantly differed from those obtained from men for certain major and trace elements (p < 0.05). Concentrations of Ca and Mg in men were significantly lower than in women (p < 0.05) and were decreasing with age (p < 0.05). CONCLUSIONS: The present investigation revealed a relationship between the elemental composition of hair and the place of permanent residence of a person, formed under the influence of regional industrial complexes, and determining gender and age-related differences. These findings enhance the possibilities of forensic human identification.

Association between ALOX15 gene polymorphism and brick-tea type skeletal fluorosis in Tibetans, Kazaks and Han, China.

To evaluate the association between ALOX15 gene polymorphism and skeletal fluorosis (SF), a case-control study was conducted. A total of 1023 individuals, including 308 Tibetans, 290 Kazaks and 425 Han, were enrolled in this study, in which cases and controls were 278 and 745, respectively. SF was diagnosed by X-ray absorptiometry. SNPs were genotyped using the Sequenom Mass ARRAY system. The genotypes of ALOX15 rs7220870, rs2664593 and rs1107852 were not associated with the risk of SF. After reconstructing the haplotype of rs7220870 and rs11078528, the risk effect of haplotype CA was found in Han participants aged ≤45 years or with moderate fluoride intake. Diplotype of CC/CC had a protective effect on SF risk in Han participants; whereas, CA/CC diplotype showed a risk effect on SF risk in participants aged ≥65; Our results provide the first evidence of an association between ALOX15 gene polymorphism and SF risk in Han participants.Abbreviation: SF: Skeletal fluorosis; SNP: Single Nucleotide polymorphism.

Genetic substructure and admixture of Mongolians and Kazakhs inferred from genome-wide array genotyping.

BACKGROUND: Mongolian populations are widely distributed geographically, showing abundant ethnic diversity with geographic and tribal differences. AIM: To infer the genetic substructure, admixture and ancient genetic sources of Mongolians together with Kazakhs. SUBJECTS AND METHODS: We genotyped more than 690,000 genome-wide SNPs from 33 Mongolian and Chinese Kazakh individuals and compared these with both ancient and present-day Eurasian populations using Principal Component Analysis (PCA), ADMIXTURE, Refine-IBD, f statistics, qpWave and qpAdm. RESULTS: We found genetic substructures within Mongolians corresponding to Ölöd, Chahar, and Inner Mongolian clusters, which was consistent with tribe classifications. Mongolian and Kazakh groups derived about 6-40% of West Eurasian related ancestry, most likely from Bronze Age Steppe populations. The East Asian related ancestry in Mongolian and Kazakh groups was well represented by the Neolithic DevilsCave related nomadic lineage, comprising 42-64% of studied groups. We also detected 10-51% of Han Chinese related ancestry in Mongolian and Kazakh groups, especially in Inner Mongolians. The average admixture times for Inner Mongolian, Mongolian_Chahar, Mongolian_Ölöd and Chinese Kazakh were about 1381, 626, 635 and 632 years ago, respectively, with Han and French as the sources. CONCLUSION: The DevilsCave related ancestry was once widespread westwards covering a wide geographical range from Far East Russia to the Mongolia Plateau. The formation of present-day Mongolic and Turkic-speaking populations has also received genetic influence from agricultural expansion.

The antibiotic knowledge, attitudes and behaviors of patients, doctors and pharmacists in the WHO Eastern European region - a qualitative, comparative analysis of the culture of antibiotic use in Armenia, Georgia, Kazakhstan, Moldova, Russia and Tajikistan.

BACKGROUND: To reduce antimicrobial resistance (AMR), initiatives such as surveillance activities and activities to increase knowledge about how and why antibiotics (ABs) are (mis)used are needed. More surveillance systems are in place in the WHO Western European region than in the Eastern region, and only sparse knowledge exists about the current culture of AB use in the Eastern European countries. OBJECTIVE: To investigate AB knowledge, attitudes and behaviors in countries in the WHO Eastern European region in order to identify overall similarities and differences across the region and how AB knowledge, attitudes and behavior patterns may be influenced by the national health care system. METHODS: Semi-structured interviews were conducted in Armenia, Georgia, Kazakhstan, Moldova, Russia and Tajikistan with patients, doctors and pharmacists. In total, 80 interviews were carried out. A directed content analysis was applied, followed by a comparative analysis, identifying the similarities and differences in AB attitudes, knowledge and behaviors between the countries and discussing how the national health care systems might influence these patterns. RESULTS: Cross-national patterns were identified regarding patients seeking ABs over-the-counter (OTC), patient variations in their requests for ABs when consulting doctors, and, finally, doctors and pharmacists appearing knowledgeable about ABs and their uses, with doctors displaying careful attitudes towards AMR. Indications of national differences between the countries included the ability of patients to afford ABs, prescribing practices of doctors and pharmacist attitudes towards selling ABs without prescriptions. Multiple aspects involved in patient and pharmacist AB decision making were detected, such as various rationales involved in buying/selling ABs OTC, implying that these processes are more complex than previously reported in the literature. CONCLUSIONS: Similarities across the Eastern European region could be seen in patient needs and uses of antibiotics obtained OTC at community pharmacies, whereas doctors appeared more influenced by specific structures of the national healthcare system.

The Health Needs of Female Labor Migrants from Central Asia in Russia.

There has been an increasing number of women migrating for work from Central Asia to Russia in recent years, yet very little is known about their specific health needs. We conducted a scoping study to understand what is known about their health and to identify the gaps and research priorities among this population. We conducted a literature review and key informant interviews. Our findings were grouped around general health issues, access to and utilization of health care services, and sexual and reproductive health concerns. Through our review, we identified the following priority research areas: stress, acculturation and process of adaptation; cultural and gender norms influencing health; contraceptive use and sexual risk behaviors; prenatal care; patient-provider communication and trust; use of informal health services; and preventative health care.

Impact of interactions among metabolic syndrome components on the development of cardiovascular disease among Kazakhs in Xinjiang.

BACKGROUND: Few prospective studies have explored the effect of interactions among metabolic syndrome (MS) components on the development of cardiovascular disease (CVD) in the Kazakh population in Xinjiang Province of China. METHOD: As of December 2016, 2,644 participants who completed a baseline survey over a period of 5 years or more were included in the study. The multiplicative interactions among MS components were evaluated by incorporation of the product terms into a logistic regression model. The additive interactions among MS components were evaluated by calculating the additive interaction index. Logistic regression was used to construct a predictive model, and CVD risk level was divided according to the risk probability of the population that did not eventually have CVD. RESULTS: When we analyzed the independent risk of MS and its components on developing CVD, only blood pressure(BP) and waist circumference(WC) were associated with CVD. A linear association was found between the risk of CVD, BP/WC, and the number of other components (trend, P<0.001). The risk of developing CVD increased when BP and WC coexisted, or when combined BP/WC with MS (≥3 components except for BP and WC) was present; however, there were no significant interactions among MS components. After the CVD hazards were divided into four levels, it was showed that over 19.92% of the incidence probability was in the population under mediate-risk while over 35.24% of them was in the high-risk group, respectively. CONCLUSIONS: BP and WC were independent risk factors for CVD in the Kazakh population. The risk of CVD was greatly increased when BP and WC coexisted or when combined BP/WC with MS (≥3 components except for BP and WC) was present, but no significant interactions were found among MS components.

A LIMA1 variant promotes low plasma LDL cholesterol and decreases intestinal cholesterol absorption.

A high concentration of low-density lipoprotein cholesterol (LDL-C) is a major risk factor for cardiovascular disease. Although LDL-C levels vary among humans and are heritable, the genetic factors affecting LDL-C are not fully characterized. We identified a rare frameshift variant in the LIMA1 (also known as EPLIN or SREBP3) gene from a Chinese family of Kazakh ethnicity with inherited low LDL-C and reduced cholesterol absorption. In a mouse model, LIMA1 was mainly expressed in the small intestine and localized on the brush border membrane. LIMA1 bridged NPC1L1, an essential protein for cholesterol absorption, to a transportation complex containing myosin Vb and facilitated cholesterol uptake. Similar to the human phenotype, Lima1-deficient mice displayed reduced cholesterol absorption and were resistant to diet-induced hypercholesterolemia. Through our study of both mice and humans, we identify LIMA1 as a key protein regulating intestinal cholesterol absorption.

FRZB1 rs2242070 polymorphisms is associated with brick tea type skeletal fluorosis in Kazakhs, but not in Tibetans, China.

Skeletal fluorosis is a metabolic bone and joint disease caused by excessive accumulation of fluoride in the bones. Compared with Kazakhs, Tibetans are more likely to develop moderate and severe brick tea type skeletal fluorosis, although they have similar fluoride exposure. Single nucleotide polymorphisms (SNPs) in frizzled-related protein (FRZB) have been associated with osteoarthritis, but their association with the risk of skeletal fluorosis has not been reported. In this paper, we investigated the association of three SNPs (rs7775, rs2242070 and rs9288087) in FRZB1with brick tea type skeletal fluorosis risk in a cross-sectional case-control study conducted in Sinkiang and Qinghai, China. A total of 598 individuals, including 308 Tibetans and 290 Kazakhs, were enrolled in this study, in which cases and controls were 221 and 377, respectively. The skeletal fluorosis was diagnosed according to the Chinese diagnostic criteria of endemic skeletal fluorosis (WS192-2008). The fluoride content in tea water or urine was detected using the fluoride ion electrode. SNPs were assessed using the Sequenom MassARRAY system. Binary logistic regressions found evidence of association with rs2242070 AA genotype in only Kazakh participants [odds ratio (OR) 0.417, 95% CI 0.216-0.807, p = 0.009], but not in Tibetans. When stratified by age, this protective effect of AA genotype in rs2242070 was pronounced in Kazakh participants aged 46-65 (OR 0.321, 95% CI 0.135-0.764, p = 0.010). This protective association with AA genotype in rs2242070 in Kazakhs also appeared to be stronger with tea fluoride intake > 3.5 mg/day (OR 0.396, 95% CI 0.182-0.864, p = 0.020). Our data suggest there might be differential genetic influence on skeletal fluorosis risk in Kazakh and Tibetan participants and that this difference might be modified by tea fluoride intake.

Inhibitory effects of candesartan on KCa3.1 potassium channel expression and cell culture and proliferation in peripheral blood CD4+T lymphocytes in Kazakh patients with hypertension from the Xinjiang region.

BACKGROUND AND AIM: Increasing evidence confirms that potassium channels are essential for lymphocyte activation, suggesting an involvement in the development of hypertension. Moreover, chronic inflammation is regarded as a direct or indirect manifestation of hypertension, highlighting the theoretical mechanisms. In this study, we investigated changes in KCa3.1 potassium channel expression in the blood of hypertensive and healthy Kazakh people in north-west China. METHODS: Flow cytometry technology was used for T-lymphocyte subtype analysis. Changes in the messenger RNA and protein expression of the KCa3.1 potassium channel in CD4+ T lymphocytes were detected using real-time quantitative polymerase chain reaction and western blots, using CD4+ T-cell samples from hypertensive Kazakh patients divided into candesartan and TRAM-34 treatment groups, and healthy case controls. Peripheral blood CD4+ T lymphocytes were activated and proliferated in vitro and then incubated for 0, 24, and 48 h under various treatment conditions. Changes in CD4+ T-lymphocytic proliferation were determined using Cell Counting Kit-8 and electron microscope photography. RESULTS: Expression of KCa3.1 was significantly higher in the hypertensive patients than in the controls (p < 0.05). Compared with the healthy group, Kazakh hypertensive patients had a reduced proportion of CD4+ T lymphocytes (p < 0.05).Candesartan and TRAM-34 intervention for 24 h and 48 h inhibited the expression of Kv1.3 and KCa3.1 at mRNA and protein level (p < 0.05). CONCLUSIONS: Increase in functional KCa3.1 channels expressed in CD4+ T lymphocytes of Kazakh patients with hypertension was blocked by candesartan, providing theoretical support for hypertension treatment at the cellular ion channel level. Candesartan may potentially regulate hypertensive inflammatory responses by inhibiting T-lymphocytic proliferation and KCa3.1 potassium channel expression in CD4 + T lymphocytes.

Prevalence, Awareness, Treatment, and Control of Hypertension among Kazakhs with high Salt Intake in Xinjiang, China: A Community-based Cross-sectional Study.

Hypertension is a leading cause of death worldwide; data on hypertension among ethnic minorities in China are sparse. This study aimed to estimate hypertension prevalence, awareness, treatment, and control in a Kazakh population, and to assess the association between salt intake and the above measures. A cross-sectional survey was conducted among Kazakh adults (≥30 years old) in the town of Hongdun, Altay, Xinjiang. Survey procedures included a questionnaire, physical measurement, and laboratory tests. Of 1805 eligible individuals, 1668 (92.4%) were included in the analysis. After adjustment for gender, age, and occupation, prevalence of hypertension was 45.5%. The proportions with awareness, treatment, control, or medication-control were 61.0%, 28.8%, 2.9% and 10.1%, respectively. Higher prevalence was seen among nomads and farmers (50.7% and 44.6%, respectively). However, the proportions with treatment or control were lower than seen among urban citizens. Hypertension prevalence was higher in those with higher salt intake (p = 0.0008). In contrast, the proportions with awareness (p = 0.0389), treatment (p = 0.0010), control (p = 0.0503), and medication-control (p = 0.2012) reduced as salt intake increased. In conclusion, hypertension prevalence is high in this population, but the proportions with awareness, treatment, or control are sub-optimal. Public health interventions that improve hypertension prevention and control, particularly among nomads, is needed.

Identification and characterization of NPC1L1 variants in Uygur and Kazakh with extreme low-density lipoprotein cholesterol.

BACKGROUND: Plasma levels of low-density lipoprotein cholesterol (LDL-C) are a major risk factor for cardiovascular disease and are influenced by both heredity and dietary habits. The Niemann-Pick C1 like 1 (NPC1L1) protein mediates efficient dietary cholesterol absorption and contributes to variations in human LDL-C levels. METHODS: In the present study, using high throughput sequencing we identified three non-synonymous (NS) variations and 64 synonymous variations in the NPC1L1 gene from subsets of Chinese Han, Uygur and Kazakh populations with high or low LDL-C. Subsequently, three NS variations encoding R174H, V177I and V1284L substitutions were observed only in Uygur and Kazakh individuals with limited maximal plasma LDL-C levels. RESULTS: In further experiments, we investigated cholesterol-regulated recycling and glycosylation and stability of these NS NPC1L1 variants. However, no significant differences between WT and variant NPC1L1 proteins were observed using in vivo assays in mouse livers with adenovirus-mediated expression, demonstrating that none of the three NPC1L1 NS variants caused decreased uptake of biliary cholesterol. CONCLUSIONS: Simultaneously, these data indicate that R174H, V177I and V1284L NPC1L1 variations in high or low LDL-C individuals may not directly influence cholesterol absorption by NPC1L1.

Regulatory Role of miR-203 in Occurrence and Progression of Kazakh Esophageal squamous cell carcinoma.

Esophageal carcinoma is one of the most common malignant tumors and the Kazakh national minority (ethnic) in Xinjiang (northwest of China) has been reported to be one of the highest incidence of Esophageal squamous cell carcinoma (ESCC) in the world. MicroRNA-203 (miR-203) was described as a tumor-suppressive miRNA in several cancers, but little study about the role of miR-203 in Kazakh ESCC. Therefore, we aimed to investigate the role of miR-203 in the occurrence and progression of Kazakh ESCC. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect miR-203 expression, and immunohistochemistry (IHC) was used to examine P63 expression. The expression level of miR-203 in ESCC was significantly lower than that of cancer adjacent normal (CAN) samples (P < 0.05). Whereas the expression level of P63 in ESCC was significantly higher than that of CAN samples (P < 0.05), an inverse association between the expression of P63 and miR-203 was found but was not statistically significant (P > 0.05). These findings suggest that miR-203 is a tumor suppressor gene that plays an important role in inhibiting the occurrence of Kazakh ESCC in Xinjiang, China.

Identification of a novel homozygous mutation in MYO3A in a Chinese family with DFNB30 non-syndromic hearing impairment.

INTRODUCTION: Hearing loss is a common sensory impairment. Several genetic loci or genes responsible for non-syndrome hearing loss have been identified, including the well-known deafness genes GJB2, MT-RNR1 and SLC26A4. MYO3A belongs to the myosin superfamily. Previously only three mutations in this gene have been found in an Isreali family with DFNB30, in which patients demonstrated progressive hearing loss. METHODS: In this study, we characterized a consanguineous Kazakh family with congenital hearing loss. By targeted sequence capture and next-generation sequencing, we identified a homozygous mutation and did bioinformatics analysis to this mutation. RESULTS: A homozygous mutation, MYO3A:c.1841C>T (p.S614F), was identified to be responsible for the disease. Ser614 is located in the motor domain of MYO3A that is highly conserved among different species. Molecular modeling predicts that the conserved Ser614 may play an important role in maintaining the stability of ß-sheet and the interaction between neighboring ß-strand. CONCLUSIONS: This is the second report on MYO3A mutations in deafness and the first report in China. The finding help facilitate establishing a better relationship between MYO3A mutation and hearing phenotypes.

Association of Insulin Resistance with Glucose and Lipid Metabolism: Ethnic Heterogeneity in Far Western China.

Objective. To study the relationships between IR and glucose and lipid metabolism in far western China and these relationships' ethnic heterogeneity. Methods. From the baseline survey, 419 Uygur cases, 331 Kazak cases, and 220 Han cases were randomly selected, resulting in a total of 970 cases for study. FINS concentration was measured by radioimmunoassay. Results. (1) In the Kazak population, IR was correlated with hyperglycemia; high levels of TC, TG, and LDL-C; and low levels of HDL-C and abdominal obesity (all P < 0.05). (2) In the Uygur population, the influence of IR on hyperglycemia and abdominal obesity was the greatest. In the Kazak population, IR was associated with hyperglycemia most closely. In the Han population, IR may have had an impact on the incidence of low HDL-C levels. (3) After adjusting for sex, age, smoking status, and alcohol consumption, IR was still associated with anomalies in the metabolism of the Uygur, Kazak, and Han populations. Conclusion. IR was involved in the process of glucose and lipid metabolism, and its degree of involvement differed among the ethnicities studied. We could consider reducing the occurrence of abnormal glucose and lipid metabolism by controlling IR and aiming to reduce the prevalence of metabolic syndrome and related diseases.

Potassium channel changes of peripheral blood T-lymphocytes from Kazakh hypertensive patients in Northwest China and the inhibition effect towards potassium channels by telmisartan.

BACKGROUND AND AIM: Increasing evidence indicates that chronic inflammation is a direct or indirect manifestation of hypertension. Potassium channels are thought to be critical for lymphocyte activation, which suggests that hypertension may be an inflammatory disease initiated at the ion channel level. METHODS: This study investigated changes in interleukin (IL)-6, IL-17, and transforming growth factor beta (TGF-b1) expression in the blood of Kazakh hypertensive patients in Northwest China using ELISA technology. Whole-cell patch clamp technology was used to evaluate current changes associated with Kv1.3 and KCa3.1 in peripheral blood T lymphocytes of hypertensive patients, and to investigate current changes induced by telmisartan. We also investigated the effects of telmisartan on expression of Kv1.3 and KCa3.1 at mRNA and protein levels in peripheral blood T lymphocytes using real-time polymerase chain reaction and Western blot analysis. RESULTS: Expression of IL-6, IL-17 and TGF-b1 in the blood of Kazakh hypertensive patients in Northwest China was significantly higher than in healthy controls (p < 0.05). The current mediated by Kv1.3 and KCa3.1 and the corresponding expression at mRNA and protein levels in T lymphocytes were also higher in these hypertensive patients than in controls (p < 0.05). Telmisartan intervention for 24 h and 48 h inhibited the current and expression of Kv1.3 and KCa3.1 at mRNA and protein levels (p < 0.05). CONCLUSIONS: These results indicated that the increase in functional Kv1.3 and KCa3.1 channels expressed in T lymphocytes of Kazakh patients with hypertension was blocked by telmisartan, resulting in a reduced inflammatory response. These results provide theoretical support for the treatment of hypertension at the cellular ion channel level.

Identification of a novel compound heterozygous mutation in PTPRQ in a DFNB84 family with prelingual sensorineural hearing impairment.

With a prevalence of 0.1 %, hearing loss is among the most common sensory impairments and affects several million people around the world. Identification of deafness-related genes or loci may facilitate basic research and clinical translational research of the disorder. The PTPRQ gene encodes protein tyrosine phosphatase receptor Q, which is required for the formation of shaft connectors and the normal maturation and development of hair bundles in the mammalian cochlea. Here, we present the genetic and molecular characteristics of a Kazakh family with an autosomal recessive non-syndromic hearing impairment, DFNB84. Using whole-exome sequencing, we identified two mutations that together form a novel compound heterozygous mutation in PTPRQ. Sanger sequencing confirmed that the affected members inherited both the c.16_17insT (L8fsX18) and c.2714delA (E909fsX922) mutations. Both mutations lead to a frameshift and a truncated form of the protein. The novel compound heterozygous mutation co-segregated with hearing loss in this family, and neither of the two mutations was found in 200 healthy Kazakh controls or in any of the public databases. In the study, we identified novel mutations in PTPRQ responsible for DFNB84. This is the third report of PTPRQ mutations involved in deafness and the first report of familial deafness in China. The identification of novel mutations in PTPRQ presented here further confirms the essential role of PTPRQ in hearing development and auditory function. Our data provide additional molecular information for establishing a better genotype-phenotype understanding of DFNB84.

Overweight, high blood pressure and impaired fasting glucose in Uyghur, Han, and Kazakh Chinese children and adolescents.

OBJECTIVES: To investigate whether the levels of blood pressure and fasting glucose differ among Chinese children of three different ethnicities (i.e., Uyghurs, Kazakhs, and Hans) and whether the differences are explained by childhood obesity. METHODS: A school-based cross-sectional study was conducted in a large three ethnic pediatric population (n = 6633), whose ages ranged from 7 to 18 years. Anthropometrics and blood pressure were measured using standard protocols. Fasting glucose was measured in a subset of children (n = 2295) who were randomly selected based on ethnicity and age. The age-sex stratified Chinese national cut-offs were used to define obesity and high blood pressure (HBP). The prevalence of HBP, impaired fasting glucose (IFG), mean levels of blood pressure, and glucose were compared among three ethnic groups. RESULTS: 2142 Uyghurs, 2078 Han, and 1997 Kazakhs were analyzed. After adjusting for age and body mass index (BMI), the mean blood pressure for Uyghurs was on average, 2-4 mm Hg lower than those for Hans and Kazakhs. Kazakhs had the lowest mean fasting glucose compared with Hans and Uyghurs (4.5 vs. 5.0 vs. 4.8 mmol/L, respectively). The differences in blood pressure and fasting glucose persisted even after adjusting for age and BMI, and the differences among ethnic groups in blood pressure levels and fasting glucose levels were observed as early as 7-9 years of age. CONCLUSIONS: The prevalence of HBP and IFG differed significantly among Uyghurs, Hans, and Kazakhs, and the ethnic differences observed in childhood were consistent with those observed in adults from the same region. While childhood obesity is a significant risk factor for hypertension and elevated glucose, the differences among ethnic groups were not explained by obesity alone.

Roles of phosphorylated JNK in esophageal squamous cell carcinomas of Kazakh ethnic.

The c-Jun NH2 -terminal kinase (JNK) signal pathway has been implicated in the growth, cellular proliferation, and apoptosis in many kinds of carcinomas. However, the role of JNK in the development of esophageal squamous cell carcinomas (ESCCs) is unknown. To investigate the role of JNK in ESCC, in vitro, esophageal cancer cell line Eca109 was pretreated using SP600125, JNK specific inhibitor, then was subjected to MTT assay to examine cellular proliferation, flow cytometric analysis to detect apoptosis and cell cycle, and wound healing assay to evaluate cell migration. Meanwhile, the mRNA and protein expression of JNK in Eca109 cells pretreated with SP600125 were examined by real-time quantitative reverse transcription PCR (qRT-PCR) and Western blotting, respectively. In vivo, 12 paired of fresh ESCC and normal adjacent tissues (NAT) from Kazakh patients were used to validate the expression of JNK by qRT-PCR and Western blotting. Furthermore, to reconfirm the expression trend of activation JNK (p-JNK), enlarged 72 paired of Kazakh's ESCC and NAT were subjected to immunohistochemistry. Our results showed that the suppression of p-JNK could lead to apoptosis and reduce proliferation in Eca109 cells. However, there was an elevated expression of p-JNK protein in NAT compared with ESCC tissues, and there was significant difference between p-JNK expression and pathological differentiation (P < 0.05) in Kazakh populations. Together, all the data we obtained in the present study indicated that the p-JNK MAPK pathway was involved in pathogenesis of Kazakh's ESCC, and played a different roles in carcinogenesis and development of Kazakh's ESCC.