Hunt S C, Stephenson S H, Hopkins P N, Hasstedt S J, Williams R R
Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City.
Hypertension. 1991 Jan;17(1):1-7. doi: 10.1161/01.hyp.17.1.1.
A 7-year prospective study of a cohort of 1,458 normotensive adults from Utah pedigrees, screened from 1980 to 1985, was done to determine whether baseline levels of sodium-lithium countertransport were associated with an increased risk of future hypertension. Subsequent new hypertension (n = 39) was ascertained in 1989 from detailed follow-up medical questionnaires (67% response). Previous segregation analyses on a subset of these pedigree members who responded (n = 342) using family relationships in addition to countertransport levels have shown statistically inferred major gene segregation of sodium-lithium countertransport levels. In the normotensive adults inferred by segregation analysis to carry the recessive major gene for high sodium-lithium countertransport, new-onset hypertension occurred in 18.8% (3 of 16) compared with 3.7% (12 of 326) in the low sodium-lithium countertransport genotype group (relative risk, 4.6 [1.6, 13.9]; p = 0.03). However, an elevated baseline sodium-lithium countertransport level without genotype information from segregation analysis did not increase the risk of future hypertension in the complete cohort of adult pedigree members (relative risk, 1.02 [0.85, 1.22]). Adjustment for other risk factors reduced the relative risk to 0.90 (0.72, 1.11). We conclude that the presence of a major gene for sodium-lithium countertransport or another closely linked gene, rather than the actual level of sodium-lithium countertransport, may increase the risk of hypertension onset. High sodium-lithium countertransport levels do not increase the risk of future hypertension for individuals in whom only polygenic and environmental effects determine sodium-lithium countertransport level.(ABSTRACT TRUNCATED AT 250 WORDS)
对1980年至1985年间从犹他州家系中筛选出的1458名血压正常的成年人进行了一项为期7年的前瞻性研究,以确定钠-锂逆向转运的基线水平是否与未来患高血压的风险增加有关。1989年,通过详细的随访医学问卷(回复率67%)确定了后续新患高血压的情况(n = 39)。此前对这些有回复的家系成员的一个子集(n = 342)进行的分离分析,除了逆向转运水平外还利用了家族关系,结果显示钠-锂逆向转运水平存在统计学推断的主基因分离现象。在通过分离分析推断携带高钠-锂逆向转运隐性主基因的血压正常成年人中,新发高血压的发生率为18.8%(16人中的3人),而在低钠-锂逆向转运基因型组中为3.7%(326人中的12人)(相对风险,4.6 [1.6, 13.9];p = 0.03)。然而,在成年家系成员的完整队列中,没有来自分离分析的基因型信息时,基线钠-锂逆向转运水平升高并不会增加未来患高血压的风险(相对风险,1.02 [0.85, 1.22])。对其他风险因素进行调整后,相对风险降至0.90(0.72, 1.11)。我们得出结论,钠-锂逆向转运的主基因或另一个紧密连锁的基因的存在,而非钠-锂逆向转运的实际水平,可能会增加高血压发病的风险。对于仅由多基因和环境效应决定钠-锂逆向转运水平的个体,高钠-锂逆向转运水平不会增加未来患高血压的风险。(摘要截短至250字)