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  • Ovid Technologies (Wolters Kluwer Health)  (33)
  • Gu, Dongfeng  (33)
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  • Ovid Technologies (Wolters Kluwer Health)  (33)
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  • 1
    Online Resource
    Online Resource
    Genome-Wide Association and Functional Studies Identify SCML4 and THSD7A as Novel Susceptibility Genes for Coronary Artery Disease
    Ovid Technologies (Wolters Kluwer Health) ; 2018
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 38, No. 4 ( 2018-04), p. 964-975
    Details
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 38, No. 4 ( 2018-04), p. 964-975
    Abstract: The genetic contribution to coronary artery disease (CAD) remains largely unclear. We combined genetic screening with functional characterizations to identify novel loci and candidate genes for CAD. Approach and Results— We performed genome-wide screening followed by multicenter validation in 8 cohorts consisting of 21 828 participants of Han ethnicity and identified 3 novel intragenic SNPs (single nucleotide polymorphisms), rs9486729 ( SCML4 [Scm polycomb group protein-like 4]; odds ratio, 1.25; 95% CI, 1.17–1.34; P =3.51×10 −11 ), rs17165136 ( THSD7A [thrombospondin type 1 domain-containing 7A]; odds ratio 1.28; 95% CI, 1.21–1.35; P 〈 1.00×10 −25 ), and rs852787 ( DAB1 [disabled-1]; odds ratio, 1.29; 95% CI, 1.21–1.38; P =2.02×10 −14 ), associated with CAD with genome-wide significance. The risk allele of rs9486729 and protective allele of rs17165136 were associated with the decreased expression of their host genes, SCML4 and THSD7A , respectively, whereas rs852787 did not have transcriptional effects on any gene. Knockdown of SCML4 activated endothelial cells by increasing the expression of IL-6 , E-selectin , and ICAM and weakened their antiapoptotic activity, whereas the knockdown of THSD7A had little effect on these endothelial cell functions but attenuated monocyte adhesion via decreasing the expression of ICAM , L-selectin , and ITGB2 . We further showed that inhibiting the expression of SCML4 exacerbated endothelial dysfunction and vascular remodeling in a rat model with partial carotid ligation. Conclusions— We identify 3 novel loci associated with CAD and show that 2 genes, SCML4 and THSD7A , make functional contributions to atherosclerosis. How rs852787 and its host gene DAB1 are linked to CAD needs further studies.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    URL: Article
    DOI: 10.1161/ATVBAHA.117.310594
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2018
    detail.hit.zdb_id: 1494427-3
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  • 2
    Online Resource
    Online Resource
    Genome-Wide Association Study Identifies 8 Novel Loci Associated With Blood Pressure Responses to Interventions in Han Chinese
    Ovid Technologies (Wolters Kluwer Health) ; 2013
    In:  Circulation: Cardiovascular Genetics Vol. 6, No. 6 ( 2013-12), p. 598-607
    Details
    In: Circulation: Cardiovascular Genetics, Ovid Technologies (Wolters Kluwer Health), Vol. 6, No. 6 ( 2013-12), p. 598-607
    Abstract: Blood pressure (BP) responses to dietary sodium and potassium intervention and cold pressor test vary considerably among individuals. We aimed to identify novel genetic variants influencing individuals’ BP responses to dietary intervention and cold pressor test. Methods and Results— We conducted a genome-wide association study of BP responses in 1881 Han Chinese and de novo genotyped top findings in 698 Han Chinese. Diet-feeding study included a 7-day low-sodium (51.3 mmol/d), a 7-day high-sodium (307.8 mmol/d), and a 7-day high-sodium plus potassium supplementation (60 mmol/d). Nine BP measurements were obtained during baseline observation and each intervention period. The meta-analyses identified 8 novel loci for BP phenotypes, which physically mapped in or near PRMT6 ( P =7.29×10 –9 ), CDCA7 ( P =3.57×10 –8 ), PIBF1 ( P =1.78×10 –9 ), ARL4C ( P =1.86×10 –8 ), IRAK1BP1 ( P =1.44×10 −10 ), SALL1 ( P =7.01×10 –13 ), TRPM8 ( P =2.68×10 –8 ), and FBXL13 ( P =3.74×10 –9 ). There was a strong dose–response relationship between the number of risk alleles of these independent single-nucleotide polymorphisms and the risk of developing hypertension during the 7.5-year follow-up in the study participants. Compared with those in the lowest quartile of risk alleles, odds ratios (95% confidence intervals) for those in the second, third, and fourth quartiles were 1.39 (0.97, 1.99), 1.72 (1.19, 2.47), and 1.84 (1.29, 2.62), respectively ( P =0.0003 for trend). Conclusions— Our study identified 8 novel loci for BP responses to dietary sodium and potassium intervention and cold pressor test. The effect size of these novel loci on BP phenotypes is much larger than those reported by the previously published studies. Furthermore, these variants predict the risk of developing hypertension among individuals with normal BP at baseline.
    Type of Medium: Online Resource
    ISSN: 1942-325X , 1942-3268
    URL: Article
    DOI: 10.1161/CIRCGENETICS.113.000307
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
    detail.hit.zdb_id: 2927603-2
    detail.hit.zdb_id: 2457085-0
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  • 3
    Online Resource
    Online Resource
    Genetic Susceptibility to Lipid Levels and Lipid Change Over Time and Risk of Incident Hyperlipidemia in Chinese Populations
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Circulation: Cardiovascular Genetics Vol. 9, No. 1 ( 2016-02), p. 37-44
    Details
    In: Circulation: Cardiovascular Genetics, Ovid Technologies (Wolters Kluwer Health), Vol. 9, No. 1 ( 2016-02), p. 37-44
    Abstract: Multiple genetic loci associated with lipid levels have been identified predominantly in Europeans, and the issue of to what extent these genetic loci can predict blood lipid levels increases over time and the incidence of future hyperlipidemia remains largely unknown. Methods and Results— We conducted a meta-analysis of genome-wide association studies of lipid levels in 8344 subjects followed by replication studies including 14 739 additional individuals. We replicated 17 previously reported loci. We also newly identified 3 Chinese-specific variants in previous regions ( HLA-C , LIPG , and LDLR ) with genome-wide significance. Almost all the variants contributed to lipid levels change and incident hyperlipidemia 〉 8.1-year follow-up among 6428 individuals of a prospective cohort study. The strongest associations for lipid levels change were detected at LPL , TRIB1 , APOA1-C3-A4-A5 , LIPC , CETP , and LDLR ( P range from 4.84×10 −4 to 4.62×10 −18 ), whereas LPL , TRIB1 , ABCA1 , APOA1-C3-A4-A5 , CETP , and APOE displayed significant strongest associations for incident hyperlipidemia ( P range from 1.20×10 −3 to 4.67×10 −16 ). The 4 lipids genetic risk scores were independently associated with linear increases in their corresponding lipid levels and risk of incident hyperlipidemia. A C -statistics analysis showed significant improvement in the prediction of incident hyperlipidemia on top of traditional risk factors including the baseline lipid levels. Conclusions— These findings identified some evidence for allelic heterogeneity in Chinese when compared with Europeans in relation to lipid associations. The individual variants and those cumulative effects were independent risk factors for lipids increase and incident hyperlipidemia.
    Type of Medium: Online Resource
    ISSN: 1942-325X , 1942-3268
    URL: Article
    DOI: 10.1161/CIRCGENETICS.115.001096
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 2927603-2
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  • 4
    Online Resource
    Online Resource
    Reproducibility of Blood Pressure Responses to Dietary Sodium and Potassium Interventions : The GenSalt Study
    Ovid Technologies (Wolters Kluwer Health) ; 2013
    In:  Hypertension Vol. 62, No. 3 ( 2013-09), p. 499-505
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 62, No. 3 ( 2013-09), p. 499-505
    Abstract: Blood pressure responses to dietary sodium and potassium interventions vary among individuals. We studied the long-term reproducibility of blood pressure responses to dietary sodium and potassium intake. We repeated the dietary sodium and potassium interventions among 487 Chinese adults 4.5 years after the original dietary intervention. The identical dietary intervention protocol, which included a 7-day low-sodium feeding (51.3 mmol/d), a 7-day high-sodium feeding (307.8 mmol/d), and a 7-day high-sodium feeding with oral potassium supplementation (60.0 mmol/d), was applied in both the initial and repeated studies. Three blood pressure measurements were obtained during each of the 3 days of baseline observation and on days 5, 6, and 7 of each intervention period. The results from the 24-hour urinary excretion of sodium and potassium showed excellent compliance with the study diet. Blood pressure responses to dietary intervention in the original and repeated studies were highly correlated. For example, the correlation coefficients (95% confidence interval) for systolic blood pressure levels were 0.77 (0.73–0.80) at baseline, 0.79 (0.75–0.82) during low sodium, 0.80 (0.77–0.83) during high sodium, and 0.82 (0.79–0.85) during high sodium and potassium supplementation interventions (all P 〈 0.0001). The correlation coefficients for systolic blood pressure changes were 0.37 (0.29–0.44) from baseline to low sodium, 0.37 (0.29–0.44) from low to high sodium, and 0.28 (0.20–0.36) from high sodium to high sodium plus potassium supplementation (all P 〈 0.0001). These data indicate that blood pressure responses to dietary sodium and potassium interventions have long-term reproducibility and stable characteristics in the general population.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/HYPERTENSIONAHA.113.01034
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
    detail.hit.zdb_id: 2094210-2
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  • 5
    Online Resource
    Online Resource
    Abstract 55: Sodium Sensitivity, Sodium Resistance, and Incidence of Hypertension
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Circulation Vol. 141, No. Suppl_1 ( 2020-03-03)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 141, No. Suppl_1 ( 2020-03-03)
    Abstract: Background: Blood pressure responses to dietary sodium intake vary among individuals. However, it is unknown whether sodium sensitivity and sodium resistance predict incidence of hypertension. Methods: We conducted a feeding study, including a 7-day low-sodium diet (51.3 mmol/day) and a 7-day high-sodium diet (307.8 mmol/day), among 1,718 Chinese individuals with normal blood pressure in 2003-2005 and follow-up studies in 2008-2009 and 2011-2012. Three blood-pressure measurements and 24-hour urinary sodium excretion were obtained on each of 3 days during baseline, low- and high-sodium interventions, and follow-up visits. Latent class models were used to identify subgroups that share a similar underlying trajectory in blood-pressure responses to dietary sodium intake. Results: Three trajectories of systolic blood pressure responses to dietary sodium intake were identified (Figure). Mean (standard deviation) changes in systolic blood pressure were -13.7 (5.5), -4.9 (3.0), and 2.4 (3.0) mmHg during the low-sodium intervention, and 11.2 (5.3), 4.4 (4.1) and -0.2 (4.1) mmHg during the high-sodium intervention ( P 〈 0.001 for group differences) in high sodium-sensitive, moderate sodium-sensitive, and sodium-resistant groups, respectively. Compared to individuals with moderate sodium sensitivity, multiple-adjusted odds ratio (95% confidence intervals) for incident hypertension were 1.44 (1.03 to 1.99) for those with high sodium sensitivity and 1.42 (1.02 to 1.97) for those with sodium resistance ( P 〈 0.001 for quadratic trend). Furthermore, a J-shaped association between systolic blood pressure responses to high sodium intake and incident hypertension was identified ( P 〈 0.001). Similar results were observed for diastolic blood pressure. Conclusions: Individuals with either high sodium sensitivity or sodium resistance are at an increased risk for developing hypertension.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.141.suppl_1.55
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
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  • 6
    Online Resource
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    Abstract P335: Salt Sensitivity and Incidence of Hypertension: The GenSalt Study
    Ovid Technologies (Wolters Kluwer Health) ; 2013
    In:  Circulation Vol. 127, No. suppl_12 ( 2013-03-26)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 127, No. suppl_12 ( 2013-03-26)
    Abstract: It is well known that blood pressure (BP) responses to dietary sodium and potassium intakes vary among individuals (salt- and potassium-sensitivity). However, it is unknown whether salt- and/or potassium-sensitivity predict the risk of hypertension. We conducted a dietary sodium and potassium intervention study among 1,906 Han Chinese in 2003-05 and followed the study participants in 2008-09 and 2011-12. The dietary intervention included a 7-day low sodium-feeding (51.3 mmol/day), a 7-day high sodium-feeding (307.8 mmol/day), and a 7-day high sodium-feeding with an oral potassium supplementation (60 mmol/day). Three BP measurements were obtained on each of the last 3 days of each intervention period at the baseline and each of the 3 days of follow-up examinations. Systolic BP responses (mean ± SD) to dietary intervention were -5.5±7.0 for low-sodium, 4.9±6.0 for high-sodium, and -3.5±5.5 for potassium-supplementation. Over an average of 7.4 years of follow-up, we identified 455 incidence hypertension cases (systolic BP≥140 mmHg and/or diastolic BP ≥90 mmHg and/or use of antihypertensive medication). The age-adjusted cumulative incidences of hypertension by the quartiles of systolic BP responses to dietary intervention were showed in the following table. These associations remained after adjustment for multiple covariates. These data indicate that BP responses to dietary sodium and potassium intervention are related to the subsequent risk of hypertension. Furthermore, our study suggests that individuals who are more sensitive to dietary sodium and potassium intake are at an increased risk for hypertension and should be target for dietary intervention.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.127.suppl_12.AP335
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
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  • 7
    Online Resource
    Online Resource
    Abstract 093: Salt-sensitivity, Salt-resistance, and Incidence of Hypertension
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Hypertension Vol. 68, No. suppl_1 ( 2016-09)
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 68, No. suppl_1 ( 2016-09)
    Abstract: It is well known that blood pressure (BP) responses to dietary sodium intake vary among individuals (salt-sensitivity and salt-resistance). However, it is unknown whether salt-sensitivity and salt-resistance predict the risk of hypertension. We conducted a dietary sodium intervention study among 1,906 Han Chinese in 2003-05 and followed the study participants in 2008-09 and 2011-12. The dietary intervention included a 7-day low-sodium feeding (51.3 mmol/day) and a 7-day high-sodium feeding (307.8 mmol/day). Three BP measurements were obtained during each of the 3 days of baseline observation and on days 5, 6, and 7 of each intervention period. We used latent class models to identify subgroups that share a similar underlying trajectory in BP responses to sodium intervention. Over an average of 7.4 years of follow-up, we identified 514 incident hypertension cases. The mean (standard deviation) change in systolic BP during low-sodium and high-sodium interventions according to salt-sensitive and -resistant groups are shown in the following table. In addition, age, sex, and baseline BP-adjusted and multiple-adjusted odds ratios (95% CI) of incident hypertension are shown in the following table. These data indicate that high responses or non-responses to dietary sodium intervention are related to the risk of hypertension. Furthermore, this is the first prospective cohort study to indicate that individuals with either salt-sensitivity or salt-resistance are at an increased risk for hypertension and should be targeted for dietary intervention.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/hyp.68.suppl_1.093
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 2094210-2
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  • 8
    Online Resource
    Online Resource
    Abstract P336: Blood Pressure Responses to Cold Pressor Test and Incidence of Hypertension: The GenSalt Study
    Ovid Technologies (Wolters Kluwer Health) ; 2013
    In:  Circulation Vol. 127, No. suppl_12 ( 2013-03-26)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 127, No. suppl_12 ( 2013-03-26)
    Abstract: The cold pressor test (CPT), which measures the response of blood pressure (BP) to the stimulus of external cold, has long been a standard test to characterize sympathetic nervous system activity and has been documented to predict cardiovascular risk. We conducted a CPT among 1,998 Han Chinese in 2003-05 and followed the study participants in 2008-09 and 2011-12 for incidence of hypertension. CPT was conducted after the participant had remained sitting for 20 minutes. The participant immersed his or her left hand in the ice water bath (3°C to 5°C) for 1 minute and BP measurements at 0, 60, 120, and 240 seconds were obtained after the left hand had been removed from the ice water bath. During the follow-up examinations, 3 BP measurements were obtained on each of 3 clinical visits. The maximum and area-under-curve (AUC) of systolic BP responses (mean ± SD) to CPT were 13.9±10.2 and 17.1±22.9 at the baseline examination. Over an average of 7.4 years of follow-up, we identified 490 incidence hypertension cases (systolic BP≥140 mmHg and/or diastolic BP ≥90 mmHg and/or use of antihypertensive medication). The age-adjusted cumulative incidences of hypertension by the quartiles of systolic BP responses to CPT were showed in the following table. These associations remained after adjustment for multiple covariates. Our study identified a strong and independent association between BP responses to CPT and subsequent incidence of hypertension. These data suggest that increased sympathetic nervous system activity may play a role in the development of hypertension.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.127.suppl_12.AP336
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
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  • 9
    Online Resource
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    Abstract P059: Reproducibility of Blood Pressure Response to Cold Pressor Test: the GenSalt Study
    Ovid Technologies (Wolters Kluwer Health) ; 2012
    In:  Circulation Vol. 125, No. suppl_10 ( 2012-03-13)
    Details
    In: Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 125, No. suppl_10 ( 2012-03-13)
    Abstract: Higher blood pressure (BP) response to cold pressor test (CPT) is associated with increased risk of hypertension and cardiovascular diseases. However, it is unknown whether BP response to CPT is a stable and reproducible trait. We repeated the CPT among 568 Han Chinese who participated in the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) four years after the original study. The same CPT protocol was applied in the original and repeated studies. BP was measured prior to and at 0, 1, 2, and 4 minutes after the participants immersed their hand in ice water (3 o C to 5 o C) for 1 minute using a standard mercury sphygmomanometer. On average, study participants were 39.0 years old and 54.0% of them were male. The mean body mass index was 23.6 kg/m 2 , systolic BP was 117.8 mmHg, and diastolic BP was 74.5 mmHg at baseline among study participants. The mean (standard deviation) of systolic BP responses at time 0 and 1 minutes, maximum responses, and area-under-the-curve during CPT were 13.3 (10.1), 4.2 (6.0), 13.6 (9.8) and 10.8 (17.6) mmHg in the original study and 11.1 (9.5), 4.1 (6.0), 11.7 (8.9), and 10.1 (17.1) mmHg in the repeated study. BP responses in the original and repeated studies were highly correlated. For example, the correlation coefficients for systolic BP responses to CPT were 0.4137 at time 0 minute, 0.3711 at time 1 minute, 0.4221 for the maximum responses, and 0.3641 for area-under-the-curve during CPT (all p 〈 0.0001). These data indicate that BP response to CPT is a stable and reproducible trait. Furthermore, BP responses to CPT may be useful for identifying individuals at high risk for hypertension.
    Type of Medium: Online Resource
    ISSN: 0009-7322 , 1524-4539
    URL: Article
    DOI: 10.1161/circ.125.suppl_10.AP059
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2012
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  • 10
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    Genome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Circulation: Cardiovascular Genetics Vol. 10, No. 2 ( 2017-04)
    Details
    In: Circulation: Cardiovascular Genetics, Ovid Technologies (Wolters Kluwer Health), Vol. 10, No. 2 ( 2017-04)
    Abstract: Genome-wide single marker and gene-based meta-analyses of long-term average (LTA) blood pressure (BP) phenotypes may reveal novel findings for BP. Methods and Results— We conducted genome-wide analysis among 18 422 East Asian participants (stage 1) followed by replication study of ≤46 629 participants of European ancestry (stage 2). Significant single-nucleotide polymorphisms and genes were determined by a P 〈 5.0×10 −8 and 2.5×10 − 6 , respectively, in joint analyses of stage-1 and stage-2 data. We identified 1 novel ARL3 variant, rs4919669 at 10q24.32, influencing LTA systolic BP (stage-1 P =5.03×10 − 8 , stage-2 P =8.64×10 − 3 , joint P =2.63×10 − 8 ) and mean arterial pressure (stage-1 P =3.59×10 − 9 , stage-2 P =2.35×10 − 2 , joint P =2.64×10 − 8 ). Three previously reported BP loci ( WBP1L , NT5C2 , and ATP2B1 ) were also identified for all BP phenotypes. Gene-based analysis provided the first robust evidence for association of KCNJ11 with LTA systolic BP (stage-1 P =8.55×10 − 6 , stage-2 P =1.62×10 − 5 , joint P =3.28×10 − 9 ) and mean arterial pressure (stage-1 P =9.19×10 − 7 , stage-2 P =9.69×10 − 5 , joint P =2.15×10 − 9 ) phenotypes. Fourteen genes ( TMEM180 , ACTR1A , SUFU , ARL3 , SFXN2 , WBP1L , CYP17A1 , C10orf32 , C10orf32 - ASMT , AS3MT , CNNM2 , and NT5C2 at 10q24.32; ATP2B1 at 12q21.33; and NCR3LG1 at 11p15.1) implicated by previous genome-wide association study meta-analyses were also identified. Among the loci identified by the previous genome-wide association study meta-analysis of LTA BP, we transethnically replicated associations of the KCNK3 marker rs1275988 at 2p23.3 with LTA systolic BP and mean arterial pressure phenotypes ( P =1.27×10 − 4 and 3.30×10 − 4 , respectively). Conclusions— We identified 1 novel variant and 1 novel gene and present the first direct evidence of relevance of the KCNK3 locus for LTA BP among East Asians.
    Type of Medium: Online Resource
    ISSN: 1942-325X , 1942-3268
    URL: Article
    DOI: 10.1161/CIRCGENETICS.116.001527
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 2927603-2
    detail.hit.zdb_id: 2457085-0
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