Large Chinese Population Research Articles

NOTCH1 Gene MicroRNA Target Variation and Ventricular Septal Defect Risk.

Birth defects, the ventricular septal defect (VSD) in particular, have major public health significance. There is evidence that genetic factors play a role in VSD risk. We report here our findings on the relationship between VSD and microRNA (miRNA)-3691-3p target sequence single-nucleotide polymorphisms (SNPs) in the 3' untranslated region of the NOTCH1 gene. Functional SNPs in NOTCH1 target sequence were screened from the SNP database. A case-control study in a large Chinese Han population sample of 350 children with VSD and 430 healthy controls examined the association between rs6563 SNPs and VSD. NOTCH1 wild and mutant recombinant expression vectors were constructed by the luciferase reporter gene system. The effects of miRNA on gene regulatory effects were also analyzed. The allelic distributions at the locus rs6563 showed statistically significant susceptibility to VSD (odds ratio [OR] = 1.502, 95% confidence interval [CI] = 1.209-1.866, p < 0.001). Compared with the subjects with G/G genotype, individuals with G/A genotype or A/A genotype showed ORs 1.414 (95% CI = 1.047-1.908, p = 0.020) and 2.366 (95% CI = 1.430-3.914, p < 0.001), respectively. The miRNA-3691-3p reduced luciferase activity of the A allele. The rs6563G > A genetic variation appears to be associated with congenital VSD through gene regulatory effects of miR-3691-3p on the NOTCH1 gene. Further studies in other population samples are called for diagnostics and public health innovation in relation to birth defects.

Coffee consumption is positively related to insulin secretion in the Shanghai High-Risk Diabetic Screen (SHiDS) Study

BackgroundIt has been proved that coffee consumption was associated with a lower risk of type 2 diabetes mellitus. But the benefit effect of coffee on hyperglycemia in Chinese population was largely unknown. Besides, the relationship of coffee intake and diabetic pathogenesis was still unclear.MethodsThe study population was selected from the Shanghai High-Risk Diabetic Screen (SHiDS) project. A total of 1328 individuals over 18 years of age who have the information of coffee intake were enrolled in the study from 2012 to 2016. Each participant finished a five-point 75 g oral glucose tolerance test and finished a standard questionnaire. Insulin resistance was evaluated by HOMA-IR and insulin secretion was evaluated by HOMA-β, Stumvoll first phase and second phase indexes.ResultsCoffee consumption group had lower plasma glucose levels at 2-h and 3-h and higher insulin levels at fasting, 30-min and 1-h during OGTT after adjustment with age, fat%, BMI, waist, tea intake, smoking habit, alcohol intake, diabetes family history and educational status (P for PG2h = 0.002; P for PG3h = 0.010; P for FIN = 0.010; P for IN30min = 0.001; P for IN1h = 0.002). Both HOMA-β and Stumvoll formula indexes were positively related to coffee consumption (P for HOMA-β = 0.033; P for Stumvoll first phase = 0.003; P for Stumvoll second phase = 0.001). Logistic regression analysis further confirmed that coffee intake was independently associated with higher levels of HOMA-β and Stumvoll insulin secretion indexes [OR (95% CI) for HOMA-β = 2.270 (1.456–3.538); OR (95% CI) for Stumvoll first phase = 2.071 (1.352–3.173); OR (95% CI) for Stumvoll second phase = 1.914 (1.260–2.906)].ConclusionsCoffee intake is independently and positively related to pancreatic beta cell function in a large high-risk diabetic Chinese population.

Intercultural challenges, intracultural practices: how Chinese and Australian students understand and experience intercultural communication at an Australian university

In recent years, over half a million Chinese students travelled abroad to study, making China the largest source of international students in the global higher education market. A large Chinese population on campus does not, however, generate prolific interactions between them and local students. Language barriers and cultural distance are frequently cited in the literature as factors that hinder communication, yet it is not clear how they actually affect the communication process. To address this gap, we utilise quantitative and qualitative data collected at one Australian university through an online survey (n = 124) and focus groups (N = 16) to investigate how Chinese international students and local students understand and experience intercultural communication. We find that both student groups are quite positive about language and cultural differences but struggle with comprehension problems and low-quality interactions. Intercultural communication requires interlocutors to establish common grounds between language and cultural variations via meaning negotiation. However, being restricted by intracultural practices and norms, students are not able to fully utilise communication techniques to fulfil this need. This, in return, affects their motivations to have further intercultural interactions. The paper concludes by discussing the implications for universities and suggestions for further research.

Effects of sex, age, sampling time, and season on thyroid-stimulating hormone concentrations: A retrospective study

BackgroundMeasuring thyroid-stimulating hormone (TSH) is essential for diagnosing and monitoring thyroid diseases. The aim of this study was to evaluate the effect of sex, age, sampling time and season on TSH in a large Chinese population and to determine which factor had the greatest impact on TSH measurement results. MethodsData were obtained from the laboratory information system from September 1, 2013 to August 31, 2016. A total of 80150 TSH measurements of outpatients were enrolled in this study. TSH was measured using a Siemens ADVIA Centaur XP automatic chemiluminescence immunoassay analyzer. Linear regression models were used to assess the association between log-transformed TSH concentrations and sex, age, sampling time and season. ResultsThe serum TSH concentrations in women were significantly higher than in men. In all subjects, serum TSH concentrations increased by 0.005 μIU/mL for each year of age. TSH concentrations showed circannual variation during the 3 consecutive years of data collection and decreased during the summer while increased during the winter. The serum TSH concentrations decreased from 7 a.m. to 1 p.m. while increased from 1 p.m. to 4 p.m. The same trend was observed in TSH concentrations for sampling time stratified by sex. Linear regression revealed that sampling time might be the major factor affecting serum TSH concentrations. ConclusionSex, age, season, and sampling time significantly affected serum TSH concentrations. Age-related alteration in serum TSH concentrations was observed in this study. Sampling time was the major factor affecting serum TSH concentrations.

A Schizophrenia-Related Genetic-Brain-Cognition Pathway Revealed in a Large Chinese Population.

BackgroundIn the past decades, substantial effort has been made to explore the genetic influence on brain structural/functional abnormalities in schizophrenia, as well as cognitive impairments. In this work, we aimed to extend previous studies to explore the internal mediation pathway among genetic factor, brain features and cognitive scores in a large Chinese dataset.MethodsGray matter (GM) volume, fractional amplitude of low-frequency fluctuations (fALFF), and 4522 schizophrenia-susceptible single nucleotide polymorphisms (SNP) from 905 Chinese subjects were jointly analyzed, to investigate the multimodal association. Based on the identified imaging-genetic pattern, correlations with cognition and mediation analysis were then conducted to reveal the potential mediation pathways.FindingsOne linked imaging-genetic pattern was identified to be group discriminative, which was also associated with working memory performance. Particularly, GM reduction in thalamus, putamen and bilateral temporal gyrus in schizophrenia was associated with fALFF decrease in medial prefrontal cortex, both were also associated with genetic factors enriched in neuron development, synapse organization and axon pathways, highlighting genes including CSMD1, CNTNAP2, DCC, GABBR2 etc. This linked pattern was also replicated in an independent cohort (166 subjects), which although showed certain age and clinical differences with the discovery cohort. A further mediation analysis suggested that GM alterations significantly mediated the association from SNP to fALFF, while fALFF mediated the association from SNP and GM to working memory performance.InterpretationThis study has not only verified the impaired imaging-genetic association in schizophrenia, but also initially revealed a potential genetic-brain-cognition mediation pathway, indicating that polygenic risk factors could exert impact on phenotypic measures from brain structure to function, thus could further affect cognition in schizophrenia.

A dense mapping study of six European AITD susceptibility regions in a large Chinese Han Cohort of Graves' disease.

We aimed to investigate the six susceptibility loci of GD identified from European population in Chinese Han population and further to estimate the genetic heterogeneity of them in stratification of our GD patients. Dense mapping studies based on GWAS. A total of 1536 GD patients and 1516 controls in GWAS stage and 1994 GD patients and 2085 controls and 5033 GD patients and 5389 controls in two replication stages. Based on our previous GWAS data, independently GD-associated SNPs in each region were identified by TagSNP analysis and logistic regression analysis. The association of these SNPs was investigated in 1994 GD patients and 2085 controls, and then, the significantly associated SNPs (P<0.05) were further genotyped in a second cohort including 5033 GD patients and 5389 controls. After the first replication stage, four SNPs from three regions with Pfirst <0.05 were further selected and genotyped in another independent cohort. The association of two SNPs with GD was confirmed in combined Chinese cohorts: rs12575636 at 11q21 (Pcombined =7.55×10-11 , OR=1.27) and rs1881145 in TRIB2 at 2p25.1 (Pcombined =5.59×10-8 , OR=1.14). Further study disclosed no significant difference for these SNPs between GD subsets. However, eQTL data revealed that SESN3 could be a potential susceptibility gene of GD in 11q21 region. Out of the six susceptibility loci of GD identified from European population, two risk loci were confirmed in a large Chinese Han population. There is variability in GD genetic susceptibility in different ethnic groups. SESN3 is a potential susceptible gene of GD in 11q21.

Genetic structure and polymorphisms of Gelao ethnicity residing in southwest china revealed by X-chromosomal genetic markers

X-chromosome short tandem repeat markers (X-STRs), due to their special inheritance models, physical location on a single chromosome and the absence of recombination in male meiosis, play an important role in forensic and population genetics. While a series of genetic analyses focusing on the genetic diversity and forensic characteristics of X-STRs are well studied for ethnically/linguistically diverse and demographically large Chinese populations, genetic evidence from Gelao ethnicity is still sparse. Here, we genotyped the first batch of 19 X-STRs in 513 Chinese Gelao individuals (265 females and 248 males), and reported genetic polymorphisms, forensic characteristics based on the single locus and seven linkage groups. DXS10135 with the highest PIC (0.9106) and LG1 (DXS10148-DXS10135-DXS8378) with the largest HD (0.9970) are polymorphic and informative. The CPDs in Gelao males and females are respectively larger than 0.999999999997095 and 0.99999999999999999999918, and the combined MECs are larger than 0.999999975715109. Subsequently, we investigated the population relationships among 14 Chinese populations based on 19 X-STRs and among 23 populations based on 11 overlapped X-STRs. Our results revealed genetic differentiations among Tibeto-Burman, Altaic and other Chinese homogenous populations, and demonstrated that Guizhou Gelao has the genetically closer relationships with Han Chinese and geographically close Guizhou Miao.

Clinical performance of non-surgical periodontal therapy in a large Chinese population with generalized aggressive periodontitis.

This study aimed to evaluate clinical performance of non-surgical periodontal treatment (NSPT) and its influential factors in a large Chinese population with generalized aggressive periodontitis (GAgP). Longitudinal periodontal examination data of 1,004 GAgP patients (numbers of patients with observation periods 6weeks~, 3months~, 6months~, 1year~, 3years~ and >5years were 203, 310, 193, 205, 70 and 23, respectively) were extracted from a hospital-based electronic periodontal charting record system and analysed by multilevel analysis. Mean probing depth (PD) and attachment loss (AL) reductions at patient level were 1.17mm and 1.07mm, respectively. Multilevel analysis demonstrated PD reductions after maintenance were mainly influenced by frequency of supportive periodontal treatment (FSPT), gender, adjunctive systemic use of antibiotics, baseline mobility, tooth type and baseline PD and bleeding index reductions were mainly influenced by FSPT, adjunctive systemic use of antibiotics, baseline AL, baseline mobility, tooth type and baseline PD. The clinical performance of NSPT on patients with GAgP was proved in the large Chinese population. Outcomes of NSPT were mainly influenced by FSPT, adjunctive systemic use of antibiotics, baseline mobility, tooth type and baseline PD.

Maternal serum arsenic level during pregnancy is positively associated with adverse pregnant outcomes in a Chinese population

Arsenic is an environmental toxicant. The association of gestational arsenic exposure with adverse pregnant outcomes remains controversial. This study was to investigate the association of serum As level with adverse pregnant outcomes in a large Chinese cohort population. Total 3194 mother-and-infant pairs were recruited from the China-Anhui Birth Cohort Study. Maternal serum arsenic (As) concentration was measured using hydride generation-atomic fluorescence spectrometry. Subjects were divided into L-As group and H-As group in accordance to the 75th percentile of serum As concentration. The associations of serum As level during gestation with adverse pregnant outcomes were analyzed. The incidence of small-for-gestational-age (SGA) newborns was elevated in H-As group compared to L-As group (9.9% vs 7.6%, P = .044). After controlling confounders and stratified analysis, the adjusted OR for SGA was significant only in girls with H-As but not in boys. Moreover, the incidence of preterm delivery (PTD) was elevated in H-As group compared to L-As group (7.0% vs 4.8%, P = .016). Further analysis found that the adjusted OR for moderate-to-late PTD was 1.47 (95%CI: 1.03, 2.09; P = .034) in H-As group as compared with L-As group. These results indicate that maternal serum As level during gestation is positively associated with adverse pregnant outcomes.

Linked 4-Way Multimodal Brain Differences in Schizophrenia in a Large Chinese Han Population

Multimodal fusion has been regarded as a promising tool to discover covarying patterns of multiple imaging types impaired in brain diseases, such as schizophrenia (SZ). In this article, we aim to investigate the covarying abnormalities underlying SZ in a large Chinese Han population (307 SZs, 298 healthy controls [HCs]). Four types of magnetic resonance imaging (MRI) features, including regional homogeneity (ReHo) from resting-state functional MRI, gray matter volume (GM) from structural MRI, fractional anisotropy (FA) from diffusion MRI, and functional network connectivity (FNC) resulted from group independent component analysis, were jointly analyzed by a data-driven multivariate fusion method. Results suggest that a widely distributed network disruption appears in SZ patients, with synchronous changes in both functional and structural regions, especially the basal ganglia network, salience network (SAN), and the frontoparietal network. Such a multimodal coalteration was also replicated in another independent Chinese sample (40 SZs, 66 HCs). Our results on auditory verbal hallucination (AVH) also provide evidence for the hypothesis that prefrontal hypoactivation and temporal hyperactivation in SZ may lead to failure of executive control and inhibition, which is relevant to AVH. In addition, impaired working memory performance was found associated with GM reduction and FA decrease in SZ in prefrontal and superior temporal area, in both discovery and replication datasets. In summary, by leveraging multiple imaging and clinical information into one framework to observe brain in multiple views, we can integrate multiple inferences about SZ from large-scale population and offer unique perspectives regarding the missing links between the brain function and structure that may not be achieved by separate unimodal analyses.

The rs696880 Polymorphism in the Nogo-A Receptor Gene (RTN4R) Is Associated With Susceptibility to Sporadic Amyotrophic Lateral Sclerosis in the Chinese Population.

Single-nucleotide polymorphisms (SNPs) in the Nogo-A receptor gene (RTN4R) have been associated with increased risk for sporadic amyotrophic lateral sclerosis (SALS) in the French population. In the present study, we investigated the associations between RTN4R tag SNPs and SALS in a large Chinese population. Four tag SNPs (rs854971, rs887765, rs696880 and rs1567871) in the RTN4R gene with an r2 threshold of 0.8 and a minor allele frequency (MAF) greater than 0.2% were selected based on Chinese population data from HapMap. A total of 499 SALS patients and 503 healthy controls were genotyped for the SNPs by SNaPshot technology. Haplotype analysis of the four SNPs was performed using the SHEsis software platform. The results showed a significant association between the rs696880 risk allele (A) and SALS in the Han Chinese population (P = 0.009, odds ratio (OR) = 1.266 [1.06–1.51]). The allele and genotype frequencies of rs854971, rs887765 and rs1567871 were not associated with SALS. The distribution of the GAAT haplotype was different between the case and control groups (P = 0.008, OR = 1.289 [1.066–1.558]). In conclusion, our study showed an association between the RTN4R SNP rs696880 and the risk of SALS in the Han Chinese population, with the A allele increasing risk.

Association of Plasma Irisin with Bone Mineral Density in a Large Chinese Population Using an Extreme Sampling Design

Irisin, a myokine produced by skeletal muscle in response to physical exercise, promotes trans-differentiation of white adipose tissue into brown adipose tissue. Recent evidences suggested that irisin also plays an important role in the control of bone metabolism. This study aimed to ascertain the relationship between plasma irisin and bone mineral density (BMD) in Chinese population by adoption of an extreme sampling method. Based on a large and screened Chinese elderly population (N = 6308), two subgroups with extremely high and low hip BMD were selected for discovery (N = 80, high vs. low BMD = 44:36) and validation (N = 60, high vs. low BMD = 30:30), respectively. Plasma irisin, P1NP, and β-CTx were measured using commercially available ELISA kits. Other metabolic parameters (e.g., blood glucose, total cholesterol and triglycerides) were collected. Student's t test and Spearman correlation analyses were conducted in SPSS. Significant difference was discovered for plasma irisin between females and age-matched males (N = 80, male vs. female = 42:38, P = 0.002). The plasma irisin levels were significantly higher in high BMD subjects than in low BMD subjects, which was observed in both discovery (P = 0.012) and validation samples (P = 0.022). However, such observation was limited to males only. Further correlation analyses in males showed that plasma irisin was correlated with BMD (r = 0.362, P = 0.025) and triglyceride (r = - 0.354, P = 0.032). Plasma irisin levels were associated with hip BMD in Chinese elderly men. This study represented the first effort of investigating the relationship of plasma irisin and BMD in elderly population. The positive correlation between plasma irisin and BMD hints intrinsic communication between muscle and bone.

Association of Thyroid Function With the Estimated Glomerular Filtration Rate in a Large Chinese Euthyroid Population

Background/Aims: We aimed to explore whether thyroid function within a normal range is associated with the estimated glomerular filtration rate (eGFR) and the incidence of chronic kidney disease (CKD) in a large Chinese population. Methods: We conducted a cross-sectional study that included 10,859 euthyroid individuals who underwent an annual regular health checkup in Jiangsu Province Official Hospital between August 2012 and August 2013. We measured the thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) levels using a Roche modular analytics E170 and then calculated the eGFR using the Chinese modified Modification of Diet in Renal Disease (CMDRD) equation. Results: In multiple linear regression models, TSH was negatively associated with eGFR after adjusting for confounding factors (β = -0.072, P = 1.994×10-22). The significance remained in both males and females. No significant association was observed between FT4 and eGFR. In the logistic regression model, we did not observe significant associations of TSH or FT3 with CKD. Participants in the highest quartile of FT4 versus the lowest quartile (reference) had an increased risk of CKD (OR = 1.763, P = 0.012). The risk of CKD was more pronounced in females with the highest quartile of FT4 (OR = 2.424, P = 0.029). Conclusion: Our findings suggest that TSH is associated with eGFR in euthyroid individuals and that higher FT4 is associated with an increased risk of CKD. More cohort studies are warranted to confirm whether the association is causal.

Infant Feeding Beliefs, Attitudes, Knowledge and Practices of Chinese Immigrant Mothers: An Integrative Review of the Literature.

Chinese are a fast-growing immigrant population group in several parts of the world (e.g., Australia, Canada, Europe, Southeast Asia, United States). Research evidence suggests that compared to non-Hispanic whites, individuals of Asian-origin including Chinese are at higher risk of developing cardiovascular disease and type 2 diabetes at a lower body mass index (BMI). These risks may be possibly due to genetic differences in body composition and metabolic responses. Despite the increasing numbers of Chinese children growing up in immigrant families and the increasing prevalence of obesity among Chinese, little research has been focused on children of Chinese immigrant families. This integrative review synthesizes the evidence on infant feeding beliefs, attitudes, knowledge and practices of Chinese immigrant mothers; highlights limitations of available research; and offers suggestions for future research. Using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, we searched four electronic academic/research databases (CINAHL, Medline, PsycINFO, and PubMed) to identify peer-reviewed, full-text papers published in English between January 2000 and September 2017. Only studies with mothers 18+ years old of normally developing infants were included. Of the 797 citations identified, 15 full-text papers were retrieved and 11 studies (8 cross-sectional studies, 3 qualitative studies) met the inclusion criteria and were included in this review. Reviewed studies revealed high initiation rates of breastfeeding, but sharp declines in breastfeeding rates by six months of age. In addition, reviewed studies revealed that the concomitantly use of breast milk and formula, and the early introduction of solid foods were common. Finally, reviewed studies identified several familial and socio-cultural influences on infant feeding beliefs and practices that may increase risk of overweight and obesity during infancy and early childhood among Chinese children of immigrant families. Nonetheless, as only 11 studies were identified and because the majority of studies (n = 8) were conducted in Australia, additional research including longitudinal studies, and studies conducted in countries with large Chinese immigrant population are needed to further identify and understand influences on Chinese immigrant mothers’ beliefs, attitudes, and practices related to infant feeding that may increase risk of child overweight and obesity. This information is needed to develop interventions tailored to the beliefs and needs of this fast-growing immigrant group and aimed at promoting healthy infant feeding practices to prevent childhood overweight and obesity.

An association study between SCFD1 rs10139154 variant and amyotrophic lateral sclerosis in a Chinese cohort

Background: A recent genome-wide association study (GWAS) demonstrated that the Sec1 family domain containing 1 (SCFD1) gene is associated with amyotrophic lateral sclerosis (ALS). The objective of our study was to investigate the association between the single nucleotide polymorphism (SNP) rs10139154 in the SCFD1 gene and ALS in a Chinese cohort.Methods: A cohort of 1074 sporadic ALS (SALS) patients from the Department of Neurology at the West China Hospital of Sichuan University were genotyped for rs10139154 using a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. In addition, 927 unrelated healthy controls (HCs) from the same region were included.Results: After adjusting for age and sex, no significant differences in the genotype distributions and allele frequencies in the allelic, additive, dominant or recessive genetic models were found between SALS and HCs and between patients with spinal onset and bulbar onset. Remarkably, rs10139154 was shown to be associated with the age at onset (AAO) of ALS patients. Consistently, ALS patients with the “CC” genotype have an earlier mean AAO than that of patients with a “CG” and “CG + GG” genotype (p = 0.002 and 0.001, respectively).Conclusion: Our results suggest that there is a lack of association of SCFD1 rs10139154 with the risk for ALS in a large Chinese population, but this variant may modulate the age of onset of ALS. These findings add further evidence to the suspected implication of the SCFD1 gene in the pathogenesis of disease in our ALS population.

Predictors of Vascular Events and Disease Transformation in Chinese Patients with Myeloproliferative Neoplasms during Long-Term Follow-up

Abstract Introduction and objectives: Myeloproliferative neoplasms (MPN) are a group of heterogeneous clonal hematopoietic disorders that comprise polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). There is an increased risk of hemorrhage, thrombosis, cardiovascular (CV) event and transformation to myelofibrosis or acute leukemia. This study aims to review the clinicopathological characteristics and outcome, and prognostic indicators in a large Chinese population of patients with MPN. Methods: Patients with the diagnosis of PV, ET, PMF and MPN-unclassifiable were recruited from 2012 to 2016 in a tertiary referral center in Hong Kong. Retrospective data from the date of diagnosis were retrieved from the clinical records and reviewed by independent investigators. Progression-free survival (PFS) was defined as the duration from diagnosis to transformation to myelofibrosis, acute leukemia or death. Overall survival (OS) was defined from the duration from diagnosis to death or last follow-up. Categorical variables were compared using Pearson's chi-square or Fisher's exact test. PFS and OS were evaluated by Kaplan-Meier analysis and were compared by log-rank test. Univariate and multivariate analyses were performed with the Cox proportional hazard model. Results: 285 patients (142 men, 143 women) were included. PV, ET, PMF and MPN-U accounted for 22%, 60.0%, 10% and 8% of cases respectively (Table 1). Cytogenetic information at diagnosis was available in 47.7% (n=136) of the patients, of which 83% (N=113) had normal karyotypes. No other recurrent chromosomal abnormalities were observed apart from loss of chromosome Y. Among 230 molecularly annotated patients, 70% (N=162) harbored JAK2 V617F mutation. In 28 JAK2 V617F negative patients, 50% (N=14) and 4% (N=1) had CALR and JAK2 exon 12 mutations respectively. 13 patients were triple negative for JAK2, CALR and MPL mutations. Of all patients, treatment included aspirin prophylaxis (92%, N=263), hydroxyurea (92%, N=261), pegylated interferon (10.5%, N=30) and ruxolitinib (6.3%, N=18). CV events were observed in 45 (16%) patients, including 21 transient ischemic attacks, 14 ischemic strokes, 7 acute myocardial infarctions and 2 acute limb ischemia. 34 (76%) events occurred at diagnosis and 11 (24%) occurred while patients were on treatment. Significant risks associated with CV events were age > 50 years (p=0.002) and hypertension (p=0.038). Diabetes mellitus (p=0.163), hyperlipidemia (p=0.699), smoking (p=0.085) and concurrent ischemic heart disease (p=0.470) were not shown to be significant. Progression to MF was observed in 17% (n=11) of PV patients (median follow-up: 14.7, 9.5-27.6 years) and 12% (n=21) of ET patients (median follow-up:10.7, 1.5 - 22.6 years). Leukemic transformation occurred in 9 patients (3%) (ET, N=3, primary MF, N=1, secondary MF, N=5) at a median follow-up of 10.4 (1.0 - 22.6) years. Age >60 years and presence of splenomegaly at diagnosis were associated with inferior PFS; and age >60 years was associated with infereior OS in PV/ET patients (Figure 1). Based on these clinical criteria, PV/ET patients were divided into 3 groups, viz., age > 60 years with splenomegaly (n=8), age 60 years and splenomegaly remained significant risks for inferior PFS in univariate analysis, whereas on multivariate analysis, splenomegaly was only the significant risk for inferior PFS(Figure 2). Conclusion: This study showed that age >50 years and hypertension were associated with increased risk of cardiovascular events in MPN patients. Age > 60 years and splenomegaly on presentation were significant risks for disease transformation in PV/ET. Download : Download high-res image (171KB) Download : Download full-size image Disclosures No relevant conflicts of interest to declare.

Thyroid Stimulating Hormone Within the Reference Range is Associated with Visceral Adiposity Index and Lipid Accumulation Product: A Population-Based Study of SPECT-China

Few studies about the relationship of thyroid stimulating hormone (TSH) level with visceral adiposity index (VAI) and lipid accumulation product (LAP) in large Chinese population are available. The aim of this study was to explore whether TSH level within the reference range was associated with these two newer reliable cardiovascular risk factors. The data were obtained from a cross-sectional study (SPECT-China study, 2014-2015), which was based on the population. Participants underwent several checkups, which included anthropometric parameters, blood pressure, TSH levels, and glucose and lipid profiles. VAI and LAP were calculated. A total of 8727 subjects were enrolled in this study. The mean age was 53.00±13.05 years. Age, female to male ratio, BMI, systolic pressure, and HOMA-IR increased along with the increasing levels of TSH (p<0.01). Analysis of lipid profile showed significantly higher serum triglycerides and LDL cholesterol levels in the higher TSH quartile (p<0.001 and p=0.028, respectively). The levels of VAI and LAP were all increased along with increasing TSH level (all p<0.001). After full adjustment, TSH levels were positively associated with VAI, LAP, and TG/HDL levels significantly (B=0.041, 0.028 and 0.037, respectively, all p<0.01). Higher TSH concentrations among the reference range were common in older people as well as in women subjects, and they were positively associated with VAI and LAP. This highlighted that even subtle variations of serum TSH within the normal range may be potential risk factors for cardiovascular diseases.

Distribution of Lewis and Secretor polymorphisms and corresponding CA19-9 antigen expression in a Chinese population.

The Lewis (FUT3) and Secretor (FUT2) genes, corresponding to secretion of Lewis ABO (H) histo‐blood group antigen CA19‐9, are highly polymorphic with differences between populations. In this study, the FUT3 and FUT2 genes in 316 Chinese participants were sequenced to detect polymorphisms, and the associated CA19‐9 antigen secretion was also measured. In total, 14 genotypes of FUT3 and 10 genotypes of FUT2 were verified. Le/Le, Le/le 59,508 and Le/le 59 were the main genotypes of FUT3 with frequencies of 53.2%, 10.7% and 3.5%, respectively. Se/Se, Se/se 385 and se 385/se 385 were the main genotypes of FUT2, with frequencies of 21.4%, 18.6% and 16.2%, respectively. The alleles le 1067 and le 508 were found extensively in the Chinese population, and the frequency of allele se 385 was shown to be higher than previously reported. Phenotype analysis revealed that 9.8% of individuals were the Lewis‐negative type and 22.5% were the secretor‐negative type. Combined phenotypes showed that 3.2% of participants were of ‘double‐negative’ phenotype (le, se) and 19.3% were of single dominant non‐secretor phenotype (Le, se). Serum Lewis antigen CA19‐9 levels were significantly different between subgroups and consistent with the defined phenotype. Our study revealed the unique distribution of Lewis and Secretor polymorphisms in a large Chinese population, and decoded the combined genotypes of the two CA19‐9‐related genes.

Association of variant in the ADIPOQ gene and functional study for its role in atherosclerosis.

The burden of atherosclerosis is heritable and associated with elevated risk of developing CVDs. Here, we evaluated genetic variants of adiponectin (ADIPOQ) gene, which has important role in anti- atherosclerosis, with risk of atherosclerosis among a large Chinese population. Our results show that rs74577862 was significantly associated with risk of atherosclerosis (OR=2.08; 95%CI=1.48-2.91; P=2.2×10-5). When stratified by atherosclerosis site, rs74577862 was associated with increased risk of both carotid atherosclerosis (OR=2.03; 95%CI=1.35-3.06; P=6.3×10-4) and coronary atherosclerosis (OR=2.11; 95%CI=1.44-3.09; P=1.1×10-4). In addition, we also carried out site-directed mutagenesis and dual-luciferase reporter assay to confirm the positive finding, which presents a significant decrease in luciferase expression for the reconstructed plasmid with rs74577862 A allele in comparison to the one with G allele (P<0.001). Real-time PCR also confirmed the findings above. These results strongly suggest that the functional SNP, ADIPOQ rs74577862 might contribute to atherosclerosis susceptibility.

Lung cancer mortality clusters in Shandong Province, China: how do they change over 40 years?

Lung cancer has long been a major health problem in China. This study aimed to examine the temporal trend and spatial pattern of lung cancer mortality in Shandong Province from 1970 to 2013. Lung cancer mortality data were obtained from Shandong Death Registration System and three nationwide retrospective cause-of-death surveys. A Purely Spatial Scan Statistics method with Discrete Poisson models was used to detect possible high-risk spatial clusters. The results show that lung cancer mortality rate in Shandong Province increased markedly from 1970-1974 (7.22 per 100,000 person-years) to 2011-2013 (56.37/100, 000). This increase was associated with both demographic and non-demographic factors. Several significant spatial clusters with high lung cancer mortality were identified. The most likely cluster was located in the northern region of Shandong Province during both 1970-1974 and 2011-2013. It appears the spatial pattern remained largely consistent over the last 40 years despite the absolute increase in the mortality rates. These findings will help develop intervention strategies to reduce lung cancer mortality in this large Chinese population.