Candidate Genes for Salt-Sensitive Hypertension in Young Male Tanzanians

我们在血压正常的坦桑尼亚年轻男性中进行了盐敏感型高血压候选基因的筛选。探讨血管紧张素转换酶(ACE)插入/缺失(VD)基因多态性与盐摄入量的关系。此外，为了研究上位性基因-基因交互作用及其对表型的影响，我们对CYP11B2 C-344T多态进行了基因分型，并在血压正常的坦桑尼亚青年男性中检测了ACE I/D和CYP11B2 C-344T多态之间的基因-基因交互作用。所有受试者均获得参与的知情同意。排除了有心血管疾病、肾脏疾病和糖尿病的受试者。65名健康男性受试者参加了为期两周的干预，包括七天的盐负荷，然后进行为期一周的利尿剂治疗。在这个方案中，受试者接受了140m…在保持日常饮食的同时，每天从清汤和盐片补充剂中摄入更多等量的氯化钠，以及每天25毫克的氢氯噻嗪。在基线和每个周期的最后一天，采集血液和24小时尿液。在每一周期结束时测量血压。据我们所知，本研究首次证实了非洲人群中ACE基因多态性与盐敏感性的关系。盐负荷后，DD型血浆血管紧张素转换酶活性显著高于其他基因型(DD；20.2±6.9，DI；16.4±5.2，II；14.5±3.7IU/L，p=0.023)，而DD、DI和II型的平均血压在盐负荷时差异无统计学意义(P>0.05)。青年男性人群盐负荷期血压变化与血管紧张素转换酶基因多态性无明显关联。为观察血管紧张素转换酶基因I/D与CYP11B2-C344T基因多态之间的交互作用，同时携带CYPI1B2-344TC/CC和ACE DD基因型者的尿钠排泄量也显著高于其他两组。当存在CYP11B2 TC/CC基因型时，尿钠排泄与心率改变显著相关。而同时携带CYP11B2-344TT和ACE DD两种基因的受试者血清ACE活性高于其他两种基因组合的受试者。然而，血清ACE活性的升高对血压和心率没有显著影响。我们的结果表明，在高盐摄入量下，ACE I/D和CYP11B2 C-344T多态之间存在基因-基因相互作用，这调节了盐在高血压中启动升压效应。它为高血压提供了一系列潜在的预防和治疗方法。较少

We performed the screening of the candidate gene for salt-sensitive hypertension in young male normotensive Tanzanians. We evaluated the relation between angiotensin converting enzyme (ACE) insertion/deletion (VD) polymorphism and excessive salt intake. Moreover, to examine the epistatic gene-gene interaction and its effect on phenotype, we genotyped polymorphisms of the the CYP11B2 C-344T polymorphism, and examined the gene-gene interactions between ACE I/D and CYP11B2 C-344T polymorphisms in young male normotensive Tanzanians.Two hundred male volunteers aged 25 to 35 were recruited from the Temeke District in Dar es Salaam. Informed consent for participation was obtained from all subjects. Subjects with cardiovascular diseases, renal diseases, and diabetes mellitus were excluded. Sixty-five, healthy male subjects participated in a 2-week intervention consisting of seven days of salt loading followed by diuretic treatment for a period of one week. In this protocol, subjects took 140 m … More Eq of NaC1 from consomme' and salt tablet supplements per day, and 25 mg of hydrochlorothiazide daily while maintaining their customary diet. At the baseline and on the last day of each period, blood and 24-hour urine were collected. Blood pressure (BP) was measured at the end point of each period. ACE DI polymorphism was detected by PCR.To our knowledge, this study demonstrates for the first time the relationship between ACE gene polymorphism and salt sensitivity in Africans. Serum ACE activity in subjects with the DD genotype was significantly high compared with other genotypes after salt loading (DD; 20.2±6.9, DI; 16.4±5.2, II; 14.5±3.7 IU/L, p=0.023); however, mean blood pressure in DD, DI and II genotypes was not significantly different in the salt-loading phase.From these results, we suggest that an interaction might exist between the ACE I/D polymorphism and ACE activity. No strong contribution was observed between blood pressure change and ACE gene polymorphism in the salt-loading phase in young male TanzaniansTo observed the interaction between the ACE I/D and the CYP11B2-C344T polymorphisms, the urinary sodium excretion in subjects with both CYPI1B2-344TC/CC and ACE DD genotypes was also notably higher than the other groups. When the CYP11B2 TC/CC genotype was present, urinary sodium excretion was significantly associated with a change of heart rate. In contrast, serum ACE activity in subjects with both CYP11B2-344TT and ACE DD genotypes was higher than in other genotype combinations. However, increases in serum ACE activity did not significantly affect blood pressure or heart rate.Our results showed a gene-gene interaction between the ACE I/D and CYP11B2 C-344T polymorphisms in response to high salt intake, which regulates the initiation of the pressor effect of salt in essential hypertension. It provides a range of potential preventive and therapeutic approaches to hypertension. Less