Associations of genetic variants in M3 receptor with blood pressure responses to salt and potassium intake / 西安交通大学学报(医学版)

【Objective】 M3 muscarinic acetylcholine receptor(M3 receptor), encoded by CHRM3 gene, is widely distributed in the cardiovascular system and plays an important role in cardiac regulation. The aim of this study was to assess the association of genetic variants in M3 receptor with blood pressure(BP) responses to controlled dietary sodium and potassium interventions. 【Methods】 A total of 333 subjects from 124 families were recruited from the rural areas of northern China. After a three-day baseline observation, they were sequentially on a seven-day low-salt diet, a seven-day high-salt diet, and a seven-day high-salt diet plus potassium supplementation. Thirteen CHRM3 single nucleotide polymorphisms(SNPs) were selected for analysis. 【Results】 SNP rs10802811 of the CHRM3 was significantly associated with diastolic BP(DBP) and mean arterial pressure(MAP) responses to both low-salt and high-salt diets while SNPs rs6429147, rs373288072, rs114677844 and rs663148 showed significant associations with systolic BP(SBP) and MAP responses to high-salt diet. In addition, SNP rs6692904 was significantly associated with SBP, DBP and MAP responses to high-salt diet with potassium supplementation. 【Conclusion】 Genetic variants in M3 receptor are significantly associated with BP responses to sodium and potassium intervention, suggesting that M3 receptor may be mechanistically involved in BP salt and potassium sensitivity.

Association of genetic variants in uromodulin with blood pressure responses to dietary salt and potassium intake / 西安交通大学学报(医学版)

【Objective】 Based on our previously established salt-sensitive hypertension cohort, we aimed to examine the association of genetic variants in uromodulin with blood pressure(BP) responses to dietary interventions of sodium and potassium intake. 【Methods】 In 2004, 514 subjects from 124 families in Mei County, Shaanxi Province, were recruited to establish the salt-sensitive hypertension study cohort. Among them, 333 non-parent subjects were selected and sequentially maintained on a normal-diet for 3 days, low-salt diet for 7 days, then a high-salt diet for 7 days and a high-salt diet with potassium supplementation for another 7 days. Thirteen single nucleotide polymorphisms(SNPs) in the uromodulin gene were genotyped on the MassARRAY platform. 【Results】 BP levels decreased from the baseline to low-salt diet, increased from low-salt to high-salt diet, and decreased again from the high-salt diet to the high-salt plus potassium supplementation intervention. SNPs rs77875418 and rs4997081 of the uromodulin gene were significantly associated with diastolic BP(DBP) and mean arterial pressure(MAP) responses to high-salt diet. In addition, SNPs rs77875418, rs79245268, rs4293393, rs6497476, rs4997081, rs13333226, and rs12917707 were significantly associated with systolic BP(SBP), DBP, and MAP responses to high-salt diet with potassium supplementation. 【Conclusion】 Genetic variants in uromodulin gene are significantly associated with BP responses to sodium and potassium supplementation, suggesting that uromodulin may be mechanistically involved in BP sodium-sensitivity and potassium-sensitivity.

Association of genetic variants in NEDD4L with blood pressure responses to dietary salt and potassium intake / 西安交通大学学报(医学版)

【Objective】 4-like protein with down-regulated expression and development in neural precursor cells (NEDD4L) plays an important role in blood pressure (BP) regulation and sodium homeostasis by regulating epithelial sodium channel protein. In this study, we aimed to explore the relationship of NEDD4L gene polymorphisms with BP responses to sodium and potassium intake. 【Methods】 In 2004, 514 subjects from 124 families in Meixian County, Shaanxi Province, were recruited to establish a salt-sensitive hypertension study cohort. All the subjects received a 3-day baseline survey, a 7-day low-salt diet, a 7-day high-salt diet, and finally a 7-day high-salt and potassium supplementation. Their BP was measured and peripheral blood samples were collected at different intervention periods. The 14 gene polymorphisms of NEDD4L gene were genotyped and analyzed by MassARRAY platform. 【Results】 BP decreased on a low-salt diet, and significantly increased on a high-salt diet, and decreased again after potassium supplementation. NEDD4L SNPs rs74408486 were significantly associated with systolic BP, diastolic BP and mean arterial pressure responses to the low-salt diet. SNPs rs292449 and rs2288775 were significantly associated with pulse pressure response to the high-salt diet. In addition, SNPs rs563283 and rs292449 were significantly associated with diastolic BP, mean arterial pressure, and pulse pressure responses to high-salt and potassium supplementation diet. 【Conclusion】 NEDD4L gene polymorphisms were significantly associated with BP responses to sodium and potassium intake, suggesting that NEDD4L gene may be involved in the development of salt sensitivity and potassium sensitivity.

Associations of genetic polymorphisms in Corin with blood pressure responses to salt and potassium intake / 西安交通大学学报(医学版)

【Objective】 Corin, a transmembrane serine protease that can cleave atrial natriuretic peptide precursor (pro-ANP) into atrial natriuretic peptide with smaller bioactive molecules, participates in the pathophysiological process of hypertension and cardiac hypertrophy. The purpose of this study was to explore the relationship of Corin gene variation with blood pressure responses to sodium and potassium dietary interventions. 【Methods】 In 2004, we recruited 514 participants from 124 families in 7 villages of Baoji, Shaanxi Province, China. All the subjects received a 3-day normal diet, a 7-day low-salt diet, a 7-day high-salt diet, and finally a 7-day high-salt and potassium supplementation. Fifteen single nucleotide polymorphisms (SNPs) of Corin gene were selected for final analysis. 【Results】 SNPs rs12509275 were significantly associated with diastolic blood pressure (DBP) response to low-salt diet, while rs3749584 was associated with pulse pressure (PP) response to low-salt diet.SNP rs3749584 and rs10517195 were significantly associated with PP response to high-salt diet. In addition,rs17654278 were significantly associated with systolic blood pressure (SBP) response to high-salt and potassium supplementation, rs2271037 was significantly correlated with DBP responses to high-salt and potassium supplementation, and rs4695253, rs12509275, rs2351783, rs36090894 were significantly associated with PP response to high-salt and potassium supplementation. 【Conclusion】 Corin gene polymorphisms were associated with blood pressure response to sodium and potassium, suggesting that Corin gene may be involved in pathophysiological process of salt sensitivity and potassium sensitivity.

Correlation between monocytes and high-density lipoprotein cholesterol ratio and coronary artery stenosis in patients with unstable angina pectoris / 西安交通大学学报(医学版)

【Objective】 To investigate the correlation of monocytes and high-density lipoprotein cholesterol ratio(MHR) and albumin with the severity of coronary artery lesions in patients with unstable angina pectoris. 【Methods】 We enrolled 342 patients with unstable angina pectoris. According to the Gensini score of their coronary angiography results, they were divided into Gensini≤ 20 group, 20<Gensini ≤40 group, and Gensini >40 group. The differences in biochemical indicators between the groups were compared, and the correlation between the different indicators and the Gensini score was analyzed. According to the MHR quartile grouping, there were differences between the comparison groups. LDL-C was divided into subgroups and then subjected to multifactor Logistic regression analysis. 【Results】 MHR differed significantly among low, moderate and high grade lesions (P<0.05). Subgroup analysis showed that in low LDL-C group, Gensini score was positively correlated with MHR(P<0.05), while in high LDL-C group, Gensini score was negatively correlated with albumin(P<0.05). Multivariate Logistic regression analysis showed that the MHR level of patients with high Gensini score was 102.375 times higher than that of patients with low Gensini score(P<0.05). In the group with high LDL-C, the serum albumin level in the group with low Gensini score was 1.431 times that in the group with high Gensini score and 1.218 times that in the group with moderate Gensini score(all P<0.05). 【Conclusion】 In patients with unstable angina pectoris, especially when LDL-C levels are not high, both high MHR and low serum albumin are independent risk factors for the severity of coronary artery disease.

Association between residual cholesterol and the risk of subclinical renal damage / 西安交通大学学报(医学版)

【Objective】 Dyslipidemia has shown to be associated with cardiovascular, metabolic and renal diseases. This study aimed to investigate the association between residual cholesterol and the risk of subclinical renal damage (SRD). 【Methods】 A total of 2 342 participants were recruited from the previously established Hanzhong Adolescent Hypertension Study cohort. According to estimated glomerular filtration rate(eGFR) and urinary albumin-to-creatine ratio(uACR), the subjects were divided into SRD group and non-SRD group. The associations of residual cholesterol with eGFR, uACR, and the risk of SRD were analyzed by multiple linear and Logistic regression analyses. 【Results】 Residual cholesterol was positively correlated with uACR(r=0.081, P<0.001) but negatively correlated with eGFR (r=-0.091, P<0.001). Multiple linear regression analysis revealed that residual cholesterol was an influencing factor of uACR (β=0.075, P<0.001) and eGFR (β=-0.027, P<0.001) after adjustment for gender, age, smoke, alcohol, exercise, BMI, hypertension, diabetes and serum uric acid. In addition, Logistic regression analysis revealed that residual cholesterol was significantly associated with the risk of SRD independently of potential confounders [OR(95% CI)=1.387 (1.113-1.728), P<0.001]. Further subgroup analysis showed that residual cholesterol was significantly associated with the risk of SRD in women but not in men. 【Conclusion】 Residual cholesterol is a contributing factor in the risk of subclinical renal damage with gender-specific association.

The correlation between blood pressure response to cold pressor test and long-term blood pressure changes / 中华内科杂志

Objective:The aim of the study was to investigate the correlation between blood pressure response to cold pressor test (CPT) and follow-up blood pressure after 8 years in subjects, and to evaluate the predictive value of CPT for long-term blood pressure levels.Methods:A total of 365 individuals from eight natural villages were enrolled by stratified cluster sampling from Mei County, Shaanxi Province in 2004. Baseline characteristics of subjects were collected and CPTs were conducted. Subjects were followed up in 2009 and 2012, respectively. According to the maximal change of systolic response (SR), the area under the curve (AUC) of systolic blood pressure change (AUC-SBP), the maximal change of diastolic response (DR) and the AUC of diastolic blood pressure change (AUC-DBP) in CPT, the individuals were divided into four quartile groups by above parameters, respectively: group Ⅰ ( P25), group Ⅱ ( P50), group Ⅲ ( P75) and group Ⅳ ( P100). The correlation between blood pressure response to CPT and the follow-up blood pressure was analyzed. Results:(1) There were no significant differences in baseline blood pressure levels and prevalence of hypertension among four quartile groups no matter it was grouped on SR, DR, AUC-SBP or AUC-DBP. (2) The prevalence of hypertension in each group from lowest ( P25) to highest ( P100) in 2012 was 25.64%, 30.67%, 38.03%, 55.74% on SR grouping ( P<0.01), and 27.5%, 29.17%, 38.46%, 57.35% on AUC-SBP grouping ( P<0.05), respectively. (3) There were no significant differences in the prevalence of hypertension among four groups in 2012 ( P>0.05) either on DR or on AUC-DBP grouping. (4) The random effects model analysis showed that the correlation coefficient between SR, AUC-SBP and long-term systolic blood pressure increase were 1.91 ( P<0.05) and 1.44 ( P<0.05), respectively, and the correlation coefficient between DR, AUC-DBP and long-term diastolic blood pressure increase were 0.82 ( P<0.05) and 0.78 ( P>0.05), respectively. Age, male, body mass index, and fasting blood glucose were independent risk factors for long-term blood pressure elevation, and age, body mass index and fasting blood glucose positively correlated with changes in long-term blood pressure (all P<0.05). Conclusion:Individual systolic blood pressure response to CPT can be used as a predictor of long-term hypertension.