Jacobson Daniel R, Alexander Alice A, Tagoe Clement, Garvey W T, Williams Scott M, Tishkoff Sara, Modiano David, Sirima Sodiomon B, Kalidi Issa, Toure Amadou, Buxbaum Joel N
Veterans Administration Boston Healthcare System and Department of Medicine Boston University School of Medicine Boston Massachusetts.
Research Service Veterans Administration Boston Healthcare System Boston Massachusetts.
Mol Genet Genomic Med. 2016 Jul 14;4(5):548-56. doi: 10.1002/mgg3.231. eCollection 2016 Sep.
Transthyretin (TTR) pV142I (rs76992529-A) is one of the 113 variants in the human TTR gene associated with systemic amyloidosis. It results from a G to A transition at a CG dinucleotide in the codon for amino acid 122 of the mature protein (TTR V122I). The allele frequency is 0.0173 in African Americans.
PCR-based assays to genotype 2767 DNA samples obtained from participants in genetic studies from various African populations supplemented with sequencing data from 529 samples within the 1000 Genomes Project.
The rs76992529-A variant allele was most prevalent (allele frequency 0.0253) in the contiguous West African countries of Sierra Leone, Guinea, Ivory Coast, Burkina Faso, Ghana, and Nigeria. In other African countries, the mean allele frequency was 0.011.
Our data are consistent with a small number of founder carriers of the amyloidogenic TTR V122I (p.Val142Ile) allele in southern West Africa, with no apparent advantage or disadvantage of an allele carrying newborn reaching adulthood. In U.S. African Americans, the allele represents a significant risk for congestive heart failure late in life. If clinical penetrance is similar in African countries with high allele frequencies, then cardiac amyloidosis could also represent a significant cause of heart disease in the elderly in those populations.
转甲状腺素蛋白（TTR）pV142I（rs76992529 - A）是人类TTR基因中与系统性淀粉样变性相关的113种变体之一。它是由成熟蛋白（TTR V122I）第122位氨基酸密码子中的CG二核苷酸处的G到A转换产生的。该等位基因在非裔美国人中的频率为0.0173。
采用基于聚合酶链反应（PCR）的检测方法对来自不同非洲人群基因研究参与者的2767份DNA样本进行基因分型，并补充了来自千人基因组计划中529份样本的测序数据。
rs76992529 - A变异等位基因在毗邻的西非国家塞拉利昂、几内亚、科特迪瓦、布基纳法索、加纳和尼日利亚最为普遍（等位基因频率为0.0253）。在其他非洲国家，平均等位基因频率为0.011。
我们的数据与西非南部少数携带淀粉样变性TTR V122I（p.Val142Ile）等位基因的奠基者携带者一致，携带该等位基因的新生儿成年后没有明显的优势或劣势。在美国非裔美国人中，该等位基因代表着晚年发生充血性心力衰竭的重大风险。如果在等位基因频率较高的非洲国家临床外显率相似，那么心脏淀粉样变性也可能是这些人群中老年人心脏病的一个重要原因。
