Pijx confers broad-spectrum seedling and panicle blast resistance by promoting the degradation of ATP ß subunit and OsRbohC-mediated ROS burst in rice.

Rice blast, caused by the fungal pathogen Magnaporthe oryzae, is one of the most important diseases of rice. Utilization of blast-resistance genes is the most economical, effective, and environmentally friendly way to control the disease. However, genetic resources with broad-spectrum resistance (BSR) that is effective throughout the rice growth period are rare. In this work, using a genome-wide association study, we identify a new blast-resistance gene, Pijx, which encodes a typical CC-NBS-LRR protein. Pijx is derived from a wild rice species and confers BSR to M. oryzae at both the seedling and panicle stages. The functions of the resistant haplotypes of Pijx are confirmed by gene knockout and overexpression experiments. Mechanistically, the LRR domain in Pijx interacts with and promotes the degradation of the ATP synthase ß subunit (ATPb) via the 26S proteasome pathway. ATPb acts as a negative regulator of Pijx-mediated panicle blast resistance, and interacts with OsRbohC to promote its degradation. Consistently, loss of ATPb function causes an increase in NAPDH content and ROS burst. Remarkably, when Pijx is introgressed into two japonica rice varieties, the introgression lines show BSR and increased yields that are approximately 51.59% and 79.31% higher compared with those of their parents in a natural blast disease nursery. In addition, we generate PPLPijx Pigm and PPLPijx Piz-t pyramided lines and these lines also have higher BSR to panicle blast compared with Pigm- or Piz-t-containing rice plants. Collectively, this study demonstrates that Pijx not only confers BSR to M. oryzae but also maintains high and stable rice yield, providing new genetic resources and molecular targets for breeding rice varieties with broad-spectrum blast resistance.

Involvement of oxytocin receptor deficiency in psychiatric disorders and behavioral abnormalities.

Oxytocin and its target receptor (oxytocin receptor, OXTR) exert important roles in the regulation of complex social behaviors and cognition. The oxytocin/OXTR system in the brain could activate and transduce several intracellular signaling pathways to affect neuronal functions or responses and then mediate physiological activities. The persistence and outcome of the oxytocin activity in the brain are closely linked to the regulation, state, and expression of OXTR. Increasing evidence has shown that genetic variations, epigenetic modification states, and the expression of OXTR have been implicated in psychiatric disorders characterized by social deficits, especially in autism. Among these variations and modifications, OXTR gene methylation and polymorphism have been found in many patients with psychiatric disorders and have been considered to be associated with those psychiatric disorders, behavioral abnormalities, and individual differences in response to social stimuli or others. Given the significance of these new findings, in this review, we focus on the progress of OXTR's functions, intrinsic mechanisms, and its correlations with psychiatric disorders or deficits in behaviors. We hope that this review can provide a deep insight into the study of OXTR-involved psychiatric disorders.

CRISPR-Cas9-mediated editing of the OsHPPD 3' UTR confers enhanced resistance to HPPD-inhibiting herbicides in rice.

This study reports the creation of herbicide-resistant rice lines via CRISPR-Cas9-mediated editing of the 3' UTR of OsHPPD. Resistance index calculations revealed that two resistant lines, TS8-2#-10 and TS8-8#-6, exhibited 4.8-fold and 3.7-fold greater resistance to HPPD-inhibiting herbicides compared with the wild type, YG3012.

PBX1-promoted SFRP4 transcription inhibits cell proliferation and epithelial-mesenchymal transition in endometrial carcinoma.

OBJECTIVE: To explore the effects and mechanisms of action of the PBX1/secreted frizzled-related protein 4 (SFRP4) axis in endometrial carcinoma (EC). METHODS: The expression of PBX1 and SFRP4 was analyzed using bioinformatics prediction, followed by validation in EC cells using quantitative reverse transcription-polymerase chain reaction and western blotting. After transduction with overexpression vectors for PBX1 and SFRP4, migration, proliferation, and invasion of EC cells were measured, accompanied by the detection of E-cadherin, Snail, N-cadherin, Vimentin, ß-catenin, GSK-3ß, and C-myc expression. The association between PBX1 and SFRP4 was validated using dual luciferase reporter gene and chromatin immunoprecipitation assays. RESULTS: PBX1 and SFRP4 were downregulated in EC cells. Overexpression of PBX1 or SFRP4 resulted in weakened cell proliferation, migration, and invasion, as well as decreased expression of Snail, N-cadherin, Vimentin, ß-catenin, GSK-3ß, and C-myc and increased expression of E-cadherin. PBX1 bound to the SFRP4 promoter and promoted its transcription. Knockdown of SFRP4 reversed the repression of overexpressed PBX1 in the malignant phenotypes and EMT of EC cells, and PBX1 repressed Wnt/ß-catenin pathway activation by upregulating SFRP4 transcription. CONCLUSION: PBX1 inhibited activation of the Wnt/ß-catenin pathway by promoting SFRP4 transcription, thereby suppressing malignant phenotypes in EC cells and the EMT process.

Cost-effectiveness of empagliflozin as a treatment for heart failure with reduced ejection fraction: an analysis from the Chinese healthcare perspective.

Background: The effect of empagliflozin on the cardiovascular outcome is consistent in heart failure with reduced ejection fraction (HFrEF) patients regardless of the presence or absence of diabetes. More evidence is needed regarding the cost-effectiveness of empagliflozin in HFrEF patients. This study sought to evaluate the economic outcomes of adding empagliflozin to the standard treatment for HFrEF patients from the perspective of the Chinese healthcare system, and thus to provide information for decision makers. Methods: Based on the EMPEROR-Reduced clinical trial and other published literature data, the direct medical costs and quality-adjusted life years (QALYs) of patients with HFrEF over a 15-year study period were simulated by a Markov model, and the incremental cost-effectiveness ratio (ICER) was calculated. The price of empagliflozin referred to the data released by Menet, the hospitalization expenses and utility values were derived from published studies in China. A one-way sensitivity analysis and probabilistic sensitivity analysis were conducted to evaluate the robustness of the model. Results: The results of the cost-effectiveness analysis showed that the cost of the combination arm was $5,220.98, with a utility of 4.86 QALYs, and the cost of the standard arm was $4,873.96, with a utility of 4.68 QALYs, which equated to an ICER of $1,893.59 per QALY gained. The subgroup analysis showed that patients with HFrEF and diabetes in empagliflozin group had a higher QALY (4.62 vs. 4.35) and a lower cost ($5,213.28 vs. $5,958.60) than standard group. The corresponding ICER for non-diabetic patients was $2,568.15 per QALY. Deterministic sensitivity analysis showed robust results. At the willingness-to-pay threshold of 3 times gross domestic product (GDP) per capita ($31,510.57), almost all of the scattered points in three scenarios were below the threshold line. Conclusions: At a willingness-to-pay threshold of $31,510.57, adding empagliflozin to standard treatment is a very cost-effective option for HFrEF patients with or without diabetes in China.

Substandard starch grain4 may function in amyloplast development by influencing starch and lipid metabolism in rice endosperm.

The amyloplast is a specialized plastid in rice endosperm cells where starch is synthesized and stored as starch granules (SGs). However, little is known about the molecular mechanism underlying amyloplast and SG development. In this study, a novel mutant (c134) demonstrating a floury endosperm with enlarged SGs and amyloplasts was identified. The floury endosperm was caused by rounder, loosely packed SG. Grain-quality profile and expression analysis showed reduced contents of total starch and amylose in the c134 mutant, as well as reduced expression of a number of genes involved in starch biosynthesis. Galactosyldiacylglycerol (GDG) content and fatty acid synthesis play important roles in plastid development, and in the c134 endosperm, an obvious decrease in GDG and various fatty acids was observed, with down-regulated expression of various genes involved in lipid biosynthesis. Furthermore, map-based cloning revealed an amino acid substitution (glycine to aspartic acid) in the substandard starch grain4 (SSG4) protein. The results of this study suggest that SSG4 influences the regulation of starch and lipid metabolism as well as amyloplast development, a finding that is useful for potential genetic improvement of rice grain quality in future starch and lipid breeding and biotechnology.

Bortezomib Inhibits Multiple Myeloma Cells by Transactivating ATF3 to Trigger miR-135a-5p- Dependent Apoptosis.

Multiple myeloma (MM) is a malignant cancer with an increasing in incidence that can be alleviated through bortezomib (BTZ) treatment. Activating transcription factor 3 (ATF3) plays a major role in cancer development. Moreover, microRNAs (miRNAs) regulate carcinogenic pathways, apoptosis, and programmed necrotic cell death. However, the detailed mechanism by which ATF3 modulates BTZ drug sensitivity/resistance remains elusive. In the current study, expression of ATF3 was significantly increased under BTZ treatment in a dose-dependent manner in MM cell lines. In addition, ATF3 could regulate cell apoptosis under BTZ treatment. The effect of ATF3 was negatively regulated by its binding miRNA, miR-135a-5p. When either ATF3 was silenced or miR-135a-5p mimics were added to MM cells, they partially lost sensitivity to BTZ treatment. This was accompanied by low levels of Noxa, CHOP, and DR5, and a decrease in mitochondrial membrane potential. These results revealed the combinatorial regulatory patterns of ATF3 and miR-135a-5p in the regulatory protein interactome, which indicated a clinical significance of the miR-135a-5p-ATF3 protein interaction network in BTZ therapy. This study provides potential evidence for further investigation into BTZ resistance.

Genomic insight into balancing high yield, good quality, and blast resistance of japonica rice.

BACKGROUND: Balancing the yield, quality and resistance to disease is a daunting challenge in crop breeding due to the negative relationship among these traits. Large-scale genomic landscape analysis of germplasm resources is considered to be an efficient approach to dissect the genetic basis of the complex traits. Central China is one of the main regions where the japonica rice is produced. However, dozens of high-yield rice varieties in this region still exist with low quality or susceptibility to blast disease, severely limiting their application in rice production. RESULTS: Here, we re-sequence 200 japonica rice varieties grown in central China over the past 30 years and analyze the genetic structure of these cultivars using 2.4 million polymorphic SNP markers. Genome-wide association mapping and selection scans indicate that strong selection for high-yield and taste quality associated with low-amylose content may have led to the loss of resistance to the rice blast fungus Magnaporthe oryzae. By extensive bioinformatic analyses of yield components, resistance to rice blast, and taste quality, we identify several superior alleles for these traits in the population. Based on this information, we successfully introduce excellent taste quality and blast-resistant alleles into the background of two high-yield cultivars and develop two elite lines, XY99 and JXY1, with excellent taste, high yield, and broad-spectrum of blast resistance. CONCLUSIONS: This is the first large-scale genomic landscape analysis of japonica rice varieties grown in central China and we demonstrate a balancing of multiple agronomic traits by genomic-based strategy.

Inhibitory role of ATF3 in gastric cancer progression through regulating cell EMT and stemness.

BACKGROUND: Gastric cancer (GC) is one of the most common cancers and the third leading cause of cancer related mortality worldwide. The 5-year survival rate is rather low owing to advanced unresectable and distant metastasis. The EMT has been widely implicated in the stemness, metastatic dormancy, and chemoresistance of different solid tumors. Given the fact that activating transcription factor-3 (ATF3) is a member of the ATF/CREB family of transcription factors and its role in regulation of GC recurrence and metastasis remain poorly understood, the aim of the present study was to investigate its potential impact in epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) properties and GC aggression. METHODS: To elucidate the potential role of ATF3 in gastric cancer, we utilized SGC-7901 and MGC-803 gastric cancer cell lines as research models and constructed stable cell lines overexpressing ATF3. We conducted a series of assays including cell proliferation, colony formation, cell migration, tumorsphere formation, and invasion to investigate the functional roles of ATF3 in stemness of gastric cancer. The possible effect of ATF3 on epithelial-mesenchymal transition (EMT) was assessed through flow cytometry and qRT-PCR. In vivo functional effect of upregulation of ATF3 on tumor growth was examined in a mouse xenograft model. RESULTS: We found that overexpression of ATF3 inhibited cell proliferation, colony formation, cell migration and invasion. In addition, up-regulation of ATF3 attenuated tumorsphere formation, cell stemness, and potentially decreased expression of EMT markers. Moreover, ATF3 overexpression inhibited tumorigenesis in mouse xenograft model. CONCLUSION: Our data suggest a suppressive role of ATF3 in gastric cancer development. Our findings will provide a potential therapeutic strategy and novel drug target for gastric cancer.

Identification and fine mapping of qPBR10-1, a novel locus controlling panicle blast resistance in Pigm-containing P/TGMS line.

Rice blast is one of the most widespread and devastating diseases in rice production. Tremendous success has been achieved in the identification and characterization of genes and quantitative trait loci (QTLs) conferring seedling blast resistance, however, genetic studies on panicle blast resistance have lagged far behind. In this study, two advanced backcross inbred sister lines (MSJ13 and MSJ18) were obtained in the process of introducing Pigm into C134S and showed significant differences in the panicle blast resistance. One F2 population derived from the crossing MSJ13/MSJ18 was used to QTL mapping for panicle blast resistance using genotyping by sequencing (GBS) method. A total of seven QTLs were identified, including a major QTL qPBR10-1 on chromosome 10 that explains 24.21% of phenotypic variance with LOD scores of 6.62. Furthermore, qPBR10-1 was verified using the BC1F2 and BC1F3 population and narrowed to a 60.6-kb region with six candidate genes predicted, including two genes encoding exonuclease family protein, two genes encoding hypothetical protein, and two genes encoding transposon protein. The nucleotide variations and the expression patterns of the candidate genes were identified and analyzed between MSJ13 and MSJ18 through sequence comparison and RT-PCR approach, and results indicated that ORF1 and ORF2 encoding exonuclease family protein might be the causal candidate genes for panicle blast resistance in the qPBR10-1 locus. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-021-01268-3.

The NAC Transcription Factors OsNAC20 and OsNAC26 Regulate Starch and Storage Protein Synthesis.

Starch and storage proteins determine the weight and quality of cereal grains. Synthesis of these two grain components has been comprehensively investigated, but the transcription factors responsible for their regulation remain largely unknown. In this study, we investigated the roles of NAM, ATAF, and CUC (NAC) transcription factors, OsNAC20, and OsNAC26 in starch and storage protein synthesis in rice (Oryza sativa) endosperm. OsNAC20 and OsNAC26 showed high levels of amino acid sequence similarity. Both were localized in the aleurone layer, starchy endosperm, and embryo. Mutation of OsNAC20 or OsNAC26 alone had no effect on the grain, while the osnac20/26 double mutant had significantly decreased starch and storage protein content. OsNAC20 and OsNAC26 alone could directly transactivate the expression of starch synthaseI (SSI), pullulanase (Pul), glutelin A1 (GluA1), glutelin B4/5 (GluB4/5), α-globulin, and 16 kD prolamin and indirectly influenced plastidial disproportionating enzyme1 (DPE1) expression to regulate starch and storage protein synthesis. Although they could also bind to the promoters of ADP-Glc pyrophosphorylase small subunit 2b (AGPS2b), ADP-Glc pyrophosphorylase large subunit 2 (AGPL2), and starch branching enzymeI (SBEI), and the expression of the three genes was largely decreased in the osnac20/26 mutant, ADP-Glc pyrophosphorylase and starch branching enzyme activities were unchanged in this double mutant. In addition, OsNAC20 and OsNAC26 are main regulators of Pul, GluB4, α-globulin, and 16 kD prolamin In conclusion, OsNAC20 and OsNAC26 play an essential and redundant role in the regulation of starch and storage protein synthesis.

DAP1 negatively regulates autophagy induced by cardamonin in SKOV3 cells.

Autophagy is closely related to the formation and development of multiple human tumors including ovarian cancer. As a major regulator of this process, the role of mTOR (mammalian target of rapamycin) has been well proven. Cardamonin, a kind of flavonoid from plants, has effects on induction of autophagy and thus antiproliferation of cancer cells. However, the detailed mechanism remains unclear. DAP1 (death-associated protein 1) is a proline-rich protein, which is involved in the regulation of cellular growth and programmed cell death including autophagy and apoptosis. The aim of this study was to investigate whether DAP1 is involved in proliferation inhibition and autophagy induced by cardamonin in tumor cells. Using online bioinformatics tools, we found that DAP1 expression is closely related to the survival of patients with ovarian cancer. Our study showed that autophagy induced by cardamonin was associated with mTOR inhibition, and DAP1 was involved in this process. Silence of DAP1 decreased cell proliferation but enhanced the antiproliferative effect of cardamonin in SKOV3 cells. The level of autophagy was elevated by DAP1 silencing in SKOV3 cells. Notably, cardamonin showed higher autophagy flux in the DAP1 small interfering RNA group. Taken together, our results implied that DAP1 negatively regulates autophagy induced by cardamonin, and it may be a potential target for ovarian cancer therapy.

Gradually Decreasing Starch Branching Enzyme Expression Is Responsible for the Formation of Heterogeneous Starch Granules.

Rice (Oryza sativa) endosperm is mainly occupied by homogeneous polygonal starch from inside to outside. However, morphologically different (heterogeneous) starches have been identified in some rice mutants. How these heterogeneous starches form remains unknown. A high-amylose rice line (TRS) generated through the antisense inhibition of starch branching synthase I (SBEI) and SBEIIb contains four heterogeneous starches: polygonal, aggregate, elongated, and hollow starch; these starches are regionally distributed in the endosperm from inside to outside. Here, we investigated the relationship between SBE dosage and the morphological architecture of heterogeneous starches in TRS endosperm from the view of the molecular structure of starch. The results indicated that their molecular structures underwent regular changes, including gradually increasing true amylose content but decreasing amylopectin content and gradually increasing the ratio of amylopectin long chain but decreasing the ratio of amylopectin short chain. Granule-bound starch synthase I (GBSSI) amounts in the four heterogeneous starches were not significantly different from each other, but SBEI, SBEIIa, and SBEIIb showed a gradually decreasing trend. Further immunostaining analysis revealed that the gradually decreasing SBEs acting on the formation of the four heterogeneous granules were mainly due to the spatial distribution of the three SBEs in the endosperm. It was suggested that the decreased amylopectin in starch might remove steric hindrance and provide extra space for abundant amylose accumulation when the GBSSI amount was not elevated. Furthermore, extra amylose coupled with altered amylopectin structure possibly led to morphological changes in heterogeneous granules.

Progress in High-Amylose Cereal Crops through Inactivation of Starch Branching Enzymes.

High-amylose cereal starches provide many health benefits for humans. The inhibition or mutation of starch branching enzyme (SBE) genes is an effective method to develop high-amylose cereal crops. This review summarizes the development of high-amylose cereal crops through the inactivation of one or more SBE isoforms or combination with other genes. This review also reveals the causes of increase in amylose content in high-amylose crops. A series of changes, including amylopectin structure, crystalline structure, thermal properties, and hydrolysis properties, occurs as amylose content increases. The different morphological starch granules nominated as heterogeneous starch granules or differently stained starch granules are detected in high-amylose cereal crops. Detailed studies on four heterogeneous starch granules in high-amylose rice, which is developed by antisense RNA inhibition of SBEI/IIb, indicate that granules with different morphologies possess various molecular structures and physicochemical and functional properties. This variation diversifies their applications in food and non-food industries. However, current knowledge regarding how these heterogeneous starch granules form and why they exhibit regional distribution in endosperm remain largely unknown.

Associations between age at menarche and menopause with cardiovascular disease, diabetes, and osteoporosis in Chinese women.

CONTEXT: Ages at menarche and menopause are associated with cardiovascular disease (CVD), diabetes, and osteoporosis in Caucasian women, but associations remain unexplored in Chinese women. OBJECTIVE: The purpose of this study was to assess associations between age at menarche and menopause with CVD, diabetes, and osteoporosis in Chinese women. DESIGN AND SETTING: A cross-sectional, population-based study was conducted in Fujian, China, from June 2011 to January 2012. PARTICIPANTS: Among 6242 women aged 21 to 92 years, 3304 postmenopausal women were enrolled, excluding premenopausal women (n = 2527), those with unreported ages at menarche and menopause (n = 138), those with unrecorded physical measurements (n = 203), and those with menarche age <8 years or >20 years (n = 70). MAIN OUTCOME MEASURES: An oral glucose tolerance test, a 12-lead resting electrocardiogram, and calcaneus quantitative ultrasound were performed. RESULTS: No significant associations were found between menarche age, diabetes, and osteoporosis (both P > .05); later menarche (>18 years) was significantly associated with lower CVD risk (odds ratio = 0.71, 95% confidence interval, 0.57-0.89; P = .002). Menopause age was not associated with diabetes; higher menopause age was associated with decreasing CVD risk (P for trend = .020) and earlier menopause (≤46 years) with significantly higher osteoporosis risk (odds ratio = 1.59, 95% confidence interval, 1.07-2.36; P = .023). CONCLUSIONS: In China, ages at menarche and menopause are not associated with diabetes. Later menarche and menopause are associated with decreasing CVD risk and earlier menopause with higher osteoporosis risk. Menarche and menopause history may help identify women with increased risk of developing CVD and osteoporosis.

Association study of genetic variants of 17 diabetes-related genes/loci and cardiovascular risk and diabetic nephropathy in the Chinese She population.

BACKGROUND: Genetic determinations are important in type 2 diabetes (T2DM) pathology. We investigated associations between genetic variants of 17 diabetes-related genes/loci, T2DM and diabetic complications in Chinese She subjects. METHODS: A comprehensive gene-based association study was conducted using 17 single nucleotide polymorphisms in Chinese She subjects with normal glucose tolerance (n = 1119), impaired glucose regulation (n = 1767), and T2DM (n = 443). We applied major abnormal Minnesota Code findings to predict cardiovascular risk and estimated glomerular filtration rate to assess kidney function. RESULTS: Nine variants in FTO rs8050136, WFS1 rs10010131, CDKN2A/B rs10811661, KCNJ11 rs5219, CDC123/CAMK1D rs12779790, JAZF1 rs864745, SLC30A8 rs13266634, CDKAL1 rs10946398, and HHEX/IDE rs5015480 were significantly associated with T2DM (P < 0.05). Single nucleotide polymorphisms in WFS1 rs10010131, CDKN2A/B rs10811661, CDC123/CAMK1D rs12779790, JAZF1 rs864745, FTO rs8050136, and HHEX/IDE rs5015480 were associated with T2DM and impaired glucose regulation. Risk alleles in WFS1 rs10010131, IGF2BP2 rs4402960, CDKAL1 rs10946398, FTO rs8050136, KCNQ1 rs2237897, and ADAMTS9 rs4607103 were significantly associated with decreased homeostatic model assessment (HOMA)-ß (P < 0.05). After adjusting for age, gender and body mass index, genetic variants JAZF1 rs864745, FTO rs8050136, and HHEX/IDE rs5015480 were significantly related to reduced estimated glomerular filtration rate (P < 0.05). Genetic variants in WFS1 rs10010131, CDKN2A/B rs10811661, CDC123/CAMID rs12779790, JAZF1 rs864745, FTO rs80501360, CDKAL1 rs10946398, and HHEX/IDE rs5015480 correlated with abnormal major Minnesota Code findings (P < 0.05). CONCLUSION: Variants in WFS1, CDKN2A/B, KCNJ11, CDC123/CAMK1D, JAZF1, SLC30A8, FTO, CDKAL1, and HHEX/IDE genes are significantly associated with T2DM in She Chinese subjects. JAZF1, FTO, CDKAL1, and HHEX/IDE are associated with diabetic nephropathy. WFS1, CDKN2A/B, CDC123/CAMK1D, JAZF1, FTO, CDKAL1, and HHEX/IDE are associated with cardiovascular risk.

Prevalence and risk factors associated with prehypertension and hypertension in the Chinese She population.

BACKGROUND: Little is known about the prevalence and cardiovascular risk factors for prehypertension and hypertension in the She ethnic minority population of Fujian province in China. METHODS AND RESULTS: Between April 2009 and September 2009, 5,523 participants of She nationality aged between 20 and 80 years participated in this survey and 5,357 were eventually enrolled in analyses. The survey was carried out to assess blood pressure and cardiovascular risk factors. The prevalence of prehypertension and hypertension was 35.87 and 38.42%, respectively, in all participants. Only 26.63% of the subjects with hypertension were aware of their diagnosis. Multivariate logistic regression showed that age, gender, overweight/obesity, dyslipidemia and alcohol use were risk factors for prehypertension, and age, overweight/obesity, dyslipidemia, alcohol use, family history of hypertension and hyperuricemia were risk factors for hypertension. The clustering of 2 and ≥ 3 risk factors was in higher proportion for subjects with hypertension and prehypertension when compared with those with prehypertension and normotension, respectively. After adjusting for other confounding factors, multivariable logistic regression showed that the greater the number of clustering cardiovascular risk factors, the greater the odds ratios for prehypertension and hypertension are. CONCLUSION: Hypertension and prehypertension were common in the She population of Fujian province. Cardiovascular risk factors cluster during prehypertension and awareness of hypertension was minimal. Early lifestyle modifications could be advocated to prevent the transition from prehypertension to hypertension and cardiovascular disease.

Diabetes and its chronic complications in the She ethnic minority group of China.

OBJECTIVE: According to recent reports, the development of type 2 diabetes in China has soared at an alarming rate. However, most of the investigations were based on Han people, who account for the majority of people in China. Little is known about the prevalence of diabetes its chronic complications in the She people, who have their own traditional lifestyle and hereditable background, different from other Asian population. The present study investigated the prevalence of type 2 diabetes and associated risk factors in the adult population of She nationals. SUBJECTS AND METHODS: A total of 5,385 participants entered into the analysis eventually, including 2,308 men and 3,077 women. An oral glucose tolerance test was performed in subjects without diagnosed diabetes. Liver function, cardiovascular risk (brachial-ankle pulse wave velocity, estimated glomerular filtration rate, and abnormal Minnesota codes findings), uric acid, and neuropathy were tested to assess the profiles of associated risks. RESULTS: In general, the self-reported diabetes rate was 9.5%. After age and sex standardization, the prevalence of diabetes was 6.1% (6.7% for men and 5.7% for women) in She Chinese people. In logistic regression models, age, family history of diabetes, alcohol use, total cholesterol, and triglycerides were all significantly associated with the risk of diabetes in this cross-sectional study (all P<0.05). In all, 47.4% had cardiovascular risks, 19.4% had liver dysfunction, and 6.2% had hyperuricemia. For women, compared with the first quartile, log-transformed homeostasis model assessment for insulin resistance of the fourth quartile was significantly higher (P<0.05), and log-transformed homeostasis model assessment for ß cells was also higher in the second, third, and fourth quartiles (all P<0.05). The prevalences of polyneuropathy in impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG/IGT, and diabetes mellitus (DM) were 16.1%, 13.1%, 18.6%, and 28.4% separately, which was higher than that in normal glucose tolerance. The prevalences of polyneuropathy in IFG/IGT and DM were higher than that in IGT. CONCLUSIONS: The present study revealed that a total of 6.1% She people suffered from type 2 diabetes, which was lower than the average level of China, but the standardized prevalence of prediabetes was higher, 20.6%. Early peripheral neuropathy screening should be performed in the prediabetes population. The Toronto Clinical Neuropathy Scoring System is convenient to assess diabetic polyneuropathy in clinical practice and should be tested regularly for people in prediabetes. Liver dysfunction, headache, and insomnia, appearing before type 2 diabetes, should be assessed regularly to avoid deterioration.

Genetic variations in CYP17A1, CACNB2 and PLEKHA7 are associated with blood pressure and/or hypertension in She ethnic minority of China.

OBJECTIVES: Two large-scale genome-wide association studies (GWAs) have identified multiple variants associated with blood pressure (BP) or hypertension. The present study was to investigate whether some variations were associated with BP traits and hypertension or even prehypertension in adult She ethnic minority of China. METHODS: The population of the present study comprised 4460 (1979 males and 2481 females, respectively) unrelated she ethnic minority based on a cross-sectional study from Ningde City in Fujian province of China. There were 1692 hypertensives, 1600 prehypertensives and 1168 normotensive controls, respectively. We genotyped 7 variants in CYP17A1, PLEKHA7, CACNB2, ATP2B1, TBX3-TBX5, CSK-ULK3 and SH2B3 reported by the previous GWAs on Europeans. All analyses were performed in an additive genetic model. RESULTS: As the minor allele of rs653178 in/near SH2B3 was very rare with the frequency of 0.018, we excluded this single nucleotide polymorphism (SNP) in the further analyses. Of the other 6 loci, linear regression analyses revealed that rs11191548 in CYP17A1 and rs11014166 in CACNB2 were significantly associated with systolic BP (ß = -1.17, P = 0.002 and ß = -0.50, P = 0.006, respectively), while only SNP rs11191548 was significantly associated with diastolic BP (ß = -0.56, P=0.002) after adjusted by age, sex and BMI. Two variants in CACNB2 and PLEKHA7 were found to be significantly related to hypertension (odds ratios [OR] and (95% confidence interval [CI]): 0.79 (0.65-0.97) and 1.19 (1.01-1.41), respectively) in logistic regression analyses after adjusted by age, sex and BMI. In addition, we found that combined risk alleles of the 6 SNPs increased risk of hypertension in a stepwise fashion (P for trend < 0.001). However, none of the 6 SNPs was significantly associated with BMI or prehypertension status. While logistic analysis showed that subjects with cumulative risk alleles more than 9 had significantly higher risk for prehypertension (adjusted OR: 3.10, P < 0.001) compared with those with risk alleles less than 4. CONCLUSIONS: We replicated that variations in CYP17A1, CACNB2 and PLEKHA7 were related to BP traits and/or hypertension in She population. In addition, although we failed to observe single gene associated with prehypertension, we first found that conjoint effect of multiple risk alleles on BP might increase the risk of progressing to prehypertension.