Genome-Wide Linkage and Positional Association Analyses Identify Associations of Novel AFF3 and NTM Genes with Triglycerides:The GenSalt Study

We conducted a genome-wide linkage scan and positional association study to identify genes and variants influencing blood lipid levels among participants of the Genetic Epidemiology Network of Salt-Sensitivity （GenSalt） study. The GenSalt study was conducted among 1906 participants from 633 Han Chinese families. Lipids were measured from overnight fasting blood samples using standard methods. Multipoint quantitative trait genome-wide linkage scans were performed on the high-density lipoprotein, low-density lipoprotein, and log- transformed triglyceride phenotypes. Using dense panels of single nucleotide polymorphisms （SNPs）, single-marker and gene-based association analyses were conducted to follow-up on promising linkage signals. Additive associations between each SNP and lipid phenotypes were tested using mixed linear regression models. Gene-based analyses were performed by combining P-values from single- marker analyses within each gene using the truncated product method （TPM）. Significant associations were assessed for replication among 777 Asian participants of the Multi-ethnic Study of Atherosclerosis （MESA）. Bonferroni correction was used to adjust for multiple testing. In the GenSalt study, suggestive linkage signals were identified at 2p11.2-2q12.1 [maximum multipoint LOD score （MML） = 2.18 at 2q11.2] and t lq24.3-11q25 （MML = 2.29 at 11q25） for the log-transformed triglyceride phenotype. Follow-up analyses of these two regions revealed gene-based associations of charged multivesicular body protein 3 （CHMP3）, ring finger protein 103 （RNF103）, AF4/FMR2 family, member 3 （AFF3）, and neurotrirnin （NTM） with triglycerides （P = 4 ×10^-4, 1.00 × 10^-5, 2.00 × 10^-5, and 1.00 × 10^-7, respectively）. Both the AFF3 and NTM triglyceride associations were replicated among MESA study participants（P = 1.00 × 10^-7 and 8.00× 10^-5, respectively）. Furthermore, NTM explained the linkage signal on chromosome 11, In conclusion, we identified novel genes associated with lipid phenotypes in linkage regions on chromosomes 2 and 11.

Genetic variants in the ADD1 and GNB3 genes and bloodpressure response to potassium supplementation

Dietary potassium-supplementation has been associated with a decreased risk of hypertension and other cardiovascular outcomes.However,blood pressure(BP)responses to potassium supplementation vary among individuals.This study was designed to examine the association between 12 single nucleotide polymorphisms(SNPs)in the adducin 1 alpha(ADD1)and guanine nucleotide binding protein(G protein)beta polypeptide 3(GNB3)genes and systolic BP(SBP),diastolic BP(DBP),and mean arterial pressure(MAP)responses to potassium-supplementation.We conducted a 7-day high-sodium intervention(307.8 mmol sodium/day)followed by a 7-day high-sodium with potassium-supplementation(60 mmol potassium/day)among 1906 Han Chinese participants from rural north China.BP measurements were obtained at the end of each intervention period using a random-zero sphygmomanometer.We identified significant associations between ADD1 variant rs17833172 and SBP,DBP,and MAP responses to potassium-supplementation(all P<0.0001)that remained significant after adjustment for multiple comparisons.In participants that were heterozygous or homozygous for the G allele of this marker,SBP,DBP,and MAP response to potassium-supplementation were–3.52(–3.82,–3.21),–1.41(–1.66,–1.15)and–2.12(–2.37,–1.87),respectively,as compared to the corresponding responses of 1.99(0.25,3.73),–0.65(–0.10,–0.21),and–0.23(–0.37,0.83),respectively,for those who were homozygous for A allele.In addition,participants with at least one copy of the G allele of rs12503220 of the ADD1 gene had significantly increased DBP and MAP response to potassium-supplementation(P=0.0041 and 0.01,respectively),which was also significant after correction for multiple testing.DBP and MAP responses to potassiumsupplementation were–1.36(–1.63,–1.10)and–2.07(–2.32,–1.82)for those with at least G allele compared to corresponding responses of 0.86(–0.68,2.40)and–0.45(–1.74,0.84)for those who were homozygous for A allele.In summary,our study identified novel associations between genetic variants of the ADD1 gene and BP response to potassium-supplementation,which could have important clinical and public health implications.Future studies aimed at replicating these novel findings are warranted.

内皮系统基因与血压改变和高血压发病的关系:盐敏感遗传流行病学研究

研究者在一个纵向家庭研究中以单标记和新基因为基础的方法探讨内皮系统基因与血压改变和高血压发病率的关系。方法：盐敏感性的遗传流行病学随访研究共纳入633个汉族家庭的1768位成员。使用随机零点血压计,获取基线和随访调查的共9次血压值。

中国人基因变异和体力活动的相互作用与血压相关

维持血压动态平衡涉及遗传和非遗传因素之间复杂的相互作用，这对明确影响血压和高血压的遗传因素有巨大的挑战。该研究选取中国农村遗传基因相对均一的一人群队列，研究基因变异与体力活动相互作用对血压的影响。方法：根据是否进行体力活动将3142名入选者进行分组（体力活动组与非体力活动组），应用广义估计方程分析收缩压和舒张压与血压调控通路中24个基因表型改变的关系[包括196单核苷酸多态性（single-nucleotide polymorphisms，SNP）]。