胡遵松
中国医学科学院阜外医院 流行病学研究部
Genetic mechanisms involved in the susceptibility to salt sensitivity have not been completely clarified. This study aimed to comprehensively examine the association between genetic variants in the cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG/PRKG) genes and blood pressure (BP) responses to dietary sodium intervention in a Chinese population. A 7-day low-sodium intervention followed by a 7-day high-sodium intervention was conducted among 1906 Han participants from rural areas of northern China. Nine BP measurements were obtained at baseline and each intervention using a random-zero sphygmomanometer. Linear mixed-effect models were used to assess the additive association of 213 tag single-nucleotide polymorphisms (SNPs) in two PRKG genes (PRKG1 and PRKG2) with salt sensitivity phenotypes. Gene-based analyses were conducted using the truncated product method. The Bonferroni method was used to adjust for multiple testing. Mean systolic BP response to low-sodium intervention significantly decreased with the number of minor T allele of marker rs10997916 in PRKG1 (P = 2.4 × 10-5). Mean systolic BP responses (95% confidence interval) among those with genotypes CC, CT, and TT were -5.6 (-6.0, -5.3), -3.7 (-4.7, -2.8), and -1.3 (-4.6, 2.0) mmHg, respectively, during the low-sodium intervention. Gene-based analyses demonstrated that PRKG1 was significantly associated with systolic BP response to low-sodium intervention (P = 1.2 × 10-3), whereas PRKG2 was nominally significantly associated with diastolic BP responses to high-sodium intervention (P = 2.6 × 10-2). The current study suggested a significant association of genetic variants in the PRKG genes with variation of BP response to dietary sodium intake in Han Chinese population. These novel findings merit further replication in future.
Journal of human hypertension 2019
Previous studies have indicated that reactive oxygen species produced by NADPH oxidase (Nox) are important risk factors of hypertension. The current study aims to examine the associations of Nox-related genes with longitudinal blood pressure (BP) changes and the risk of incident hypertension in the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) follow-up study. A total of 1,768 participants from 633 families were included in our analysis. Nine BP measurements were obtained in the morning at baseline and during two follow-up visits. The mixed-effect models were used to investigate the associations of 52 tagged single-nucleotide polymorphisms in 11 Nox-related genes with BP changes and incident hypertension. Gene-based analyses were performed by truncated product method (TPM) and Versatile Gene-based Association Study (VEGAS). Over the 7.2 years of follow-up, systolic BP (SBP) and diastolic BP (DBP) increased, and 32.1% (512) of participants developed hypertension. SNPs rs12094228, rs16861188 and rs12066019 in NCF2 were significantly associated with longitudinal change in SBP (Pinteraction = 1.1 × 10-3, 2.8 × 10-3 and 1.2 × 10-3, respectively). Gene-based analyses revealed that NCF2 was significantly associated with SBP (PTPM = 1.00 × 10-6, PVEGAS = 1.26 × 10-4) and DBP changes (PTPM = 5.84 × 10-4, PVEGAS = 1.04 × 10-3). These findings suggested that NCF2 may play an important role in BP changes over time in the Han Chinese population.
Journal of human hypertension 2018
BACKGROUND AND AIMS:Dysregulation of long non-coding RNAs (lncRNAs) has been proven to be involved in the pathogenesis of coronary artery disease (CAD). However, it remains to be extensively explored. Thus, the present study aims to study expression patterns, biological functions, and diagnostic value of lncRNAs in CAD.METHODS:Using microarray, we performed the transcriptome-wide lncRNA and mRNAs expression profile of peripheral blood mononuclear cells (PBMCs) of 93 CAD patients and 48 healthy controls. Gene Ontology (GO) and pathway analysis for differentially expressed mRNAs were used to investigate underlying biological associations of differentially expressed lncRNAs, and path-net was created to depict interactions of significant pathways. qRT-PCR was used to validate selected lncRNAs in 412 CAD patients and 295 healthy controls. Receiver operating characteristic (ROC) curve analysis was performed to evaluate whether lncRNAs could be used in the diagnosis of CAD patients. Finally, the functional significance of validated lncRNAs was determined in THP-1-derived macrophages.RESULTS:We identified 1210 lncRNAs and 890 mRNAs differentially expressed from the expression profile and validated 7 lncRNAs. Two novel lncRNA biomarkers, ENST00000444488.1 and uc010yfd.1, together with CAD risk factors, had the better performance for discrimination of CAD patients from healthy controls, and ENST00000444488.1 could diagnose acute myocardial infarction (AMI) patients. The knockdown of 20 ENST00000444488.1, uc010yfd.1, ASO3973 and ENST00000602558.1 affected the expression of inflammation-related genes and their nearby genes in THP-1-derived macrophages, respectively.CONCLUSIONS:We offered a transcriptome-wide overview of aberrantly expressed lncRNAs in CAD patients, and identified two novel lncRNA biomarkers for diagnosing CAD. Loss of validated lncRNAs regulated the expression of inflammation-related genes and their nearby genes.
Atherosclerosis 2018
BACKGROUND:The aim of this study was to comprehensively test the associations of genetic variants of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-related genes with blood pressure (BP) responses to dietary sodium intervention in a Chinese population.METHODS:We conducted a 7-day low-sodium intervention followed by a 7-day high-sodium intervention among 1,906 participants in rural China. BP measurements were obtained at baseline and each dietary intervention using a random-zero sphygmomanometer. Linear mixed-effect models were used to assess the additive associations of 63 tag single-nucleotide polymorphisms in 11 NADPH oxidase-related genes with BP responses to dietary sodium intervention. Gene-based analyses were conducted using the truncated product method. The Bonferroni method was used to adjust for multiple testing in all analyses.RESULTS:Systolic BP (SBP) response to high-sodium intervention significantly decreased with the number of minor T allele of marker rs6967221 in RAC1 (P = 4.51 × 10-4). SBP responses (95% confidence interval) for genotypes CC, CT, and TT were 5.03 (4.71, 5.36), 4.20 (3.54, 4.85), and 0.56 (-1.08, 2.20) mm Hg, respectively, during the high-sodium intervention. Gene-based analyses revealed that RAC1 was significantly associated with SBP response to high-sodium intervention (P = 1.00 × 10-6) and diastolic BP response to low-sodium intervention (P = 9.80 × 10-4).CONCLUSIONS:These findings suggested that genetic variants of NADPH oxidase-related genes may contribute to the variation of BP responses to sodium intervention in Chinese population. Further replication of these findings is warranted.
American journal of hypertension 2017
BACKGROUND:We aimed to examine the associations of voltage-dependent calcium-channel genes CACNA1A and CACNA1C with blood pressure (BP) changes and hypertension incidence in a longitudinal family study.METHODS:A total of 1,768 Han Chinese participants from the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) follow-up study were eligible for the current study. Nine BP measurements were obtained at baseline and each follow-up visit using a random-zero sphygmomanometer. Mixed-effect models were used to assess additive associations of 176 tag single-nucleotide polymorphisms (SNPs) in CACNA1A and CACNA1C with longitudinal BP changes and hypertension incidence. The truncated product method was used for gene-based analysis. The Bonferroni correction was used for adjustment of multiple testing.RESULTS:During an average of 7.2 years of follow-up, 512 (32.1%) participants developed hypertension. CACNA1A SNP rs8182538 was significantly associated with longitudinal diastolic BP (DBP) change after Bonferroni correction ( Pinteraction = 9.90×10 -5 ), with mean DBP increases of 0.85, 1.03, and 1.19mm Hg per year for participants with genotypes C/C , C/T , and T/T , respectively. A similar trend was observed for the association of rs8182538 with systolic BP (SBP) change. In the gene-based analysis, CACNA1A and CACNA1C were significantly associated with DBP change ( P = 2.0×10 -5 ) and SBP change ( P = 1.4×10 -4 ) after Bonferroni correction, respectively. The gene-based associations remained significant after removing rs8182538 within CACNA1A and rs758116 within CACNA1C in sensitivity analysis.CONCLUSIONS:Our findings indicated that CACNA1A and CACNA1C might contribute to BP changes over time in Han Chinese population. Further replication of these findings is warranted.
American journal of hypertension 2016
BACKGROUND:The association between habitual caffeine intake with incident atrial fibrillation (AF) was unknown. We conducted a meta-analysis to investigate the association between chronic exposure of caffeine and the risk of AF and to evaluate the potential dose-response relation.METHODS:We searched PubMed, EMBASE, and the Cochrane Library up to November 2013 and references of relevant retrieved articles. Prospective cohort studies were included with relative risk (RR) or hazard ratio and 95% confidence intervals (CIs) for AF according to coffee/caffeine intake.RESULTS:Six prospective cohort studies with 228,465 participants were included. In the primary meta-analysis, caffeine exposure was weakly associated with a reduced risk of AF (RR, 0.90; 95% CI, 0.81-1.01; P = 0.07; I(2) = 73%). In subgroup analyses, pooled results from studies with adjustment of potential confounders showed an 11% reduction for low doses (RR, 0.89; 95% CI, 0.80-0.99, P = 0.032; I(2) = 30.9%, P = 0.227) and 16% for high doses (RR, 0.84; 95% CI, 0.75-0.94, P = 0.002; I(2) = 24.1%, P = 0.267) of caffeine consumption in AF risk. An inverse relation was found between habitual caffeine intake and AF risk (P for overall trend = 0.015; P for nonlinearity = 0.27) in dose-response meta-analysis and the incidence of AF decreased by 6% (RR, 0.94; 95% CI, 0.90-0.99) for every 300 mg/d increment in habitual caffeine intake.CONCLUSIONS:It is unlikely that caffeine consumption causes or contributes to AF. Habitual caffeine consumption might reduce AF risk.
The Canadian journal of cardiology 2014
