McCaffery Jeanne M, Bleil Maria, Pogue-Geile Michael F, Ferrell Robert E, Manuck Stephen B
Centers for Behavioral and Preventive Medicine, Brown Medical School and The Miriam Hospital, Providence, RI 02903, USA.
Psychosom Med. 2003 Sep-Oct;65(5):721-8. doi: 10.1097/01.psy.0000088585.67365.1d.
To examine the effect of length variation in the serotonin transporter gene-linked polymorphic region (5-HTTLPR) on individual differences in cardiovascular response to psychological challenge.
Heart rate (HR) and systolic and diastolic blood pressure (SBP, DBP) responses to computerized versions of two psychological challenges, the Stroop Color-Word Interference Test and mental arithmetic, were measured among 131 monozygotic (MZ) and 60 dizygotic (DZ) male or female (same-sex) European-American twin pairs. Among the 382 participants, 140 were homozygous for the "long" allele (l/l) at 5-HTTLPR, 61 were homozygous for the "short" allele (s/s), and 181 participants had one long and one short allele (l/s). Association and sib-pair analyses were performed to characterize genetic associations.
In the full sample, 5-HTTLPR was associated with HR reactivity to psychological challenge, albeit in interaction with sex. Task-elicited HR responses of women homozygous for the short allele were significantly greater than among: a) men of the same genotype; and b) women having either one (l/s) or two (l/l) long alleles at 5-HTTLPR. SBP and DBP responsivity was unrelated to genotype. These results were corroborated on reanalysis in two genetically independent subsamples. Variability at 5-HTTLPR also predicted HR reactivity in sib-pair analyses among DZ twins.
These results suggest that the commonly observed sex difference in HR reactivity may be, in part, genetically mediated and perhaps occur only among individuals homozygous for the short allele at 5-HTTLPR.
研究血清素转运体基因连锁多态性区域（5-HTTLPR）的长度变异对心血管系统应对心理挑战时个体差异的影响。
对131对单卵（MZ）和60对双卵（DZ）的欧美同性双胞胎进行测试，测量他们在面对两种心理挑战（即斯特鲁普色词干扰测试和心算）的计算机化版本时的心率（HR）、收缩压（SBP）和舒张压（DBP）反应。在382名参与者中，140人在5-HTTLPR位点为“长”等位基因纯合子（l/l），61人为“短”等位基因纯合子（s/s），181人有一个长等位基因和一个短等位基因（l/s）。进行关联分析和同胞对分析以确定基因关联。
在整个样本中，5-HTTLPR与心理挑战引起的心率反应相关，尽管存在性别交互作用。短等位基因纯合子女性的任务诱发心率反应显著高于：a）相同基因型的男性；b）在5-HTTLPR位点有一个（l/s）或两个（l/l）长等位基因的女性。收缩压和舒张压反应性与基因型无关。在两个基因独立的子样本中重新分析得到了这些结果的证实。在双卵双胞胎的同胞对分析中，5-HTTLPR的变异性也预测了心率反应性。
这些结果表明，常见的心率反应性性别差异可能部分由基因介导，并且可能仅发生在5-HTTLPR位点短等位基因纯合的个体中。
