| 1. Genetic Variants in the ADD1 and GNB3 Genes and Blood Pressure Reactions to the Cold Pressor Test (Section 1)ObjectiveWe examine the association between twelve single nucleotide polymorphisms (SNPs) in the alpha-adducin (ADD1) and guanine nucleotide binding protein (G protein) beta polypeptide 3 (GNB3) genes and systolic (SBP), diastolic (DBP) blood pressure responses to the cold pressor test (CPT).MethodsCPT was conducted in the Genetic Epidemiology Network of Salt-Sensitivity (the GenSalt) study in rural areas of northern China. Among the 2006 eligible participants aged 18-60 years,1998 (99.6%) completed the CPT and were included in the current analysis. BP measurements were obtained before and after the CPT using a random-zero sphygmomanometer according to standard protocol. SNPlex was used for the genotyping of 12 SNPs on ADD1 and GNB3. The association between SNP genotypes and BP responses to CPT were assessed on 4 genetic models (codominant, additive, dominant and recessive) using a mixed linear model.ResultsMarkers rs17833172 and rs3775067 of the ADD1 gene and markers rs4963516 of the GNB3 gene were significantly associated with blood pressure responses to CPT in at least one of the genetic models tested (P<0.05). After adjustment for multiple comparisons, SNP rs17833172 remained significantly associated with SBP responses to CPT in both the codominant and recessive genetic models (FDR p-values<0.05). Compared with the G allele carriers, the AA homozygotes of ADD1 gene had a significantly decreased SBP response to the CPT. For participants with the AA genotype, percent DBP responses and 95%CI were 4.86(2.89,6.83), compared to corresponding responses of 11.34(10.84,11.84) among participants with the GG or GA genotype.ConclusionWe found SNP rs17833172 and rs3775067 of the ADD1 gene and SNP rs4963516 of the GNB3 gene were significantly associated with blood pressure responses to CPT. After adjustment for multiple comparisons, SNP rs17833172 remained significantly associated with SBP responses to CPT. 2. Body weight and Cardiovascular Disease in Chinese Adults (Section 2 and Section 3) ObjectiveIn a large population-based prospective cohort study of Chinese adult, we analyzed the relationship between body mass index (BMI) with CVD mortality and all-cause mortality among patients with cardiovascular disease (CVD), investigated the relationship between BMI and the risk of CVD, and examined the interaction of BMI and blood pressure on the risk of CVD.MethodsSBP, DBP, height, weight and other variables were measured in China National Hypertension Survey Epidemiology Follow-up Study (CHEFS) among 169,871 Chinese men and women aged 40 years or older in 1991 using standard protocols. Follow-up evaluation was conducted in 1999-2000, with a response rate of 93.4%. Data were analyzed with Cox proportional hazards models.ResultsAmong 4192 CVD patients, after adjusted for age, gender, cigarette smoking, alcohol consumption, high school education, physical inactivity, geographic region, and urbanization, underweight men (BMI<18.5 kg/m2) have high risk for all-cause mortality, and underweight women have high relative risk for CVD mortality and all-cause mortality, meanwhile, overweight (BMI,24.0-27.9 kg/m2) and obese (BMI>28 kg/m2) men and women have no higher risk for CVD mortality and all-cause mortality than normal-weight ones (BMI,18.5-23.9 kg/m2).Compared with the normal-weight men (BMI between 18.5 and 23.9 kg/m2), underweight, overweight and obese men have relative risk and 95%CI as:1.12(0.82-1.54),0.81(0.67-1.00) and 0.77(0.57-1.00) for CVD mortality, respectively; 1.45(1.12-1.87),0.87(0.74-1.03) and 0.86(0.68-1.09) for all-cause mortality, respecitively. Compared with the normal-weight women, underweight, overweight and obese women have relative risk and 95%CI as: 1.60(1.10-2.32),0.92(0.70-1.20) and 0.91(0.67-1.25) for CVD mortality, respectively; 1.57(1.16-2.12),0.75(0.59-0.94) and 0.81(0.63-1.05) for all-cause mortality, respecitively. Among participants without CVD, after adjusted for age, gender, cigarette smoking, alcohol consumption, high school education, physical inactivity, geographic region, and urbanization, we found underweight, overweight and obese men have high risk of CVD. Compared with the normal-weight group, underweight, overweight and obese men have relative risks and 95%CI as:1.39(1.28-1.50),1.16(1.08-1.24) and 1.23(1.10-1.37). Underweight women have high risk of CVD, but overweight and obese women have no higher risk of CVD than normal-weight women. Comparing the normal-weight women, underweight, overweight and obese women have relative risks and 95%CI as: 1.32(1.21-1.44),0.93(0.86-1.00) and 1.05(0.95-1.16).After adjusted for age, gender, cigarette smoking, alcohol consumption, high school education, physical inactivity, geographic region, and urbanization, we found that the effects of systolic or diastolic BP on risk of CVD generally increased with the increasing BMI levels (underweight, normal, overweight, and obese). For example, hazards ratios (HRs) and 95% confidence interval (CI) per 1-standard deviation (SD) increase in SBP within corresponding BMI levels were 1.27(1.21-1.33),1.45(1.41-1.48),1.52 (1.45-1.59) and 1.63 (1.51-1.76), respectively. Statistically significant interactions (P<0.0001) were observed between SBP, DBP and BMI in relation to CVD. At baseline hypertensive participants we found both obese men and women had higher risk of CVD than normal-weight persons. The multivariate-adjusted relative risks (95%CI) were 1.23(1.03-1.47) and 1.20(1.02-1.40), respectively.ConclusionAmong patients with CVD, underweight was associated with increased risk of all-cause mortality in men, and increased risk of CVD mortality and all-cause mortality in women, meanwhile, overweight and obesity was not associated with risk of CVD mortality or all-cause mortality both in men and women. Among participants without CVD, we found underweight was associated with risk of CVD. Overwight and obesity was also associated with increased risk of CVD in men, but not associated with risk of CVD in women.Our findings suggest that the magnitude of the association between BP and CVD generally increase with increasing BMI. Hypertension should be regarded a more serious risk factor in obese than in lean or normal-weight persons in Chinese adults. |
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