Candidate Genes for Salt-Sensitive Hypertension in Young Male Tanzanians

我们在血压正常的年轻男性坦桑尼亚人中筛选盐敏感性高血压的候选基因。我们评估血管紧张素转换酶（ACE）插入/缺失（VD）多态性与过量盐摄入的关系。此外，为了研究上位性基因-基因相互作用及其对表型的影响，我们对CYP 11B 2 C-344 T多态性进行了基因分型，并在血压正常的年轻男性坦桑尼亚人中研究了ACE I/D和CYP 11B 2 C-344 T多态性之间的基因-基因相互作用。获得所有受试者的参与知情同意书。排除患有心血管疾病、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2周的干预，包括7天的盐负荷，然后进行为期一周的利尿剂治疗。在该方案中，受试者服用140米 ...更多信息 每天从清汤和盐片补充剂中摄入等量NaCl，每天摄入25 mg氢氯噻嗪，同时维持其常规饮食。在基线和每个阶段的最后一天，采集血液和24小时尿液。在每个周期结束时测量血压（BP）。本研究首次证实了ACE基因多态性与非洲人盐敏感性的关系。盐负荷后DD型受试者血清ACE活性显著高于其他基因型受试者（DD; 20.2±6.9，DI; 16.4±5.2，II; 14.5±3.7 IU/L，p=0.023）;然而，在盐负荷期，DD、DI和II基因型的平均血压没有显著差异。从这些结果来看，提示ACE基因I/D多态性与ACE活性之间可能存在交互作用。在坦桑尼亚青年男性中，ACE基因多态性与血压变化无显著相关性。在CYP 11B 2 - 344 TC/CC基因型和ACE DD基因型的个体中，尿钠排泄量也显著高于其他组，从而观察到ACE I/D和CYP 11B 2-C344 T基因型之间的相互作用。当CYP 11B 2 TC/CC基因型存在时，尿钠排泄与心率变化显著相关。相反，CYP 11B 2 - 344 TT和ACE DD基因型的受试者血清ACE活性高于其他基因型组合。然而，血清ACE活性的增加并没有显着影响血压或heartrate.Our研究结果表明，ACE I/D和CYP 11B 2 C-344 T多态性之间的基因相互作用，在高盐摄入量，调节盐的升压作用在原发性高血压的启动。它为高血压提供了一系列潜在的预防和治疗方法。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