Significance of the amyloidogenic transthyretin Val 122 Ile allele in African Americans in the Arteriosclerosis Risk in Communities (ARIC) and Cardiovascular Health (CHS) Studies
Significance of the amyloidogenic transthyretin Val 122 Ile allele in African Americans in the Arteriosclerosis Risk in Communities (ARIC) and Cardiovascular Health (CHS) Studies
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DOI：
10.1016/j.ahj.2010.02.006
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发表时间：
2010-05-01
影响因子：
4.8
通讯作者：
Kitzman, Dalane
中科院分区：
文献类型：
--
作者：
Buxbaum, Joel;Alexander, Alice;Kitzman, Dalane
背景：许多非洲裔美国人携带淀粉样蛋白转甲状腺素突变（TTR V122I）， 65岁后发生心脏TTR淀粉样蛋白沉积的风险很高。我们希望确定在社区居住的非裔美国人的等位基因频率及其临床外显率。方法纳入2个心血管风险社区研究（CHS和ARIC）的5000名年龄在41 ~ 93岁的非裔美国人。进行了以下工作：对储存的DNA进行TTR V122I等位基因状态的基因分型，并审查CHS和ARIC数据库中的心血管和人口统计学参数，对淀粉样变性等位基因携带者和对照组的充血性心力衰竭频率、生存率和心脏淀粉样变性特征的发生进行统计比较。结果3712名ARIC和805名CHS非裔美国人中分别有119人（3.23%）和17人（2.12%）携带TTR V122I。65岁后，V122I等位基因携带者的充血性心力衰竭频率（38% vs 15%，相对危险度2.62,P = 0.04）和死亡率（76% vs 53%，相对危险度1.46,P = 0.08）高于年龄、性别和种族匹配的对照组。在ARIC（所有科目）
Background Many African Americans carry an amyloidogenic transthyretin mutation (TTR V122I), with a high risk for cardiac TTR amyloid deposition after the age of 65 years. We wished to determine the allele frequency and its clinical penetrance in community-dwelling African Americans.Methods Five thousand consenting African Americans, aged 41 to 93 years, in 2 community studies of cardiovascular risk (CHS and ARIC) were included in the study. The following were performed: genotyping of banked DNA for TTR V122I allele status and review of cardiovascular and demographic parameters in CHS and ARIC databases, with statistical comparisons of the frequency of congestive heart failure, survival, and occurrence of features of cardiac amyloidosis in carriers of the amyloidogenic allele and controls.Results One hundred nineteen (3.23%) of 3,712 ARIC and 17 (2.12%) of 805 CHS African Americans carried TTR V122I. After the age of 65 years (CHS), the frequencies of congestive heart failure (38% vs 15%, relative risk 2.62, P = .04) and mortality (76% vs 53%, relative risk 1.46, P = .08) were higher in V122I allele carriers than in age-, gender-and ethnically matched controls. In ARIC (all subjects