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硫酸化药物遗传学:白种人、中国人和非裔美国人中SULT1A1和SULT1A2等位基因频率

Sulfation pharmacogenetics: SULT1A1 and SULT1A2 allele frequencies in Caucasian, Chinese and African-American subjects.

作者信息

Carlini E J, Raftogianis R B, Wood T C, Jin F, Zheng W, Rebbeck T R, Weinshilboum R M

机构信息

Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Medical School/Mayo Graduate School/Mayo Clinic, Rochester, MN 55905, USA.

出版信息

Pharmacogenetics. 2001 Feb;11(1):57-68. doi: 10.1097/00008571-200102000-00007.

Abstract

Sulfotransferase (SULT) enzymes catalyze the sulfate conjugation of drugs, other xenobiotics, neurotransmitters and hormones. The genes for SULT1A1 and SULT1A2 contain common genetic polymorphisms that are associated with individual variations in levels of enzyme activity as well as variations in biochemical and physical properties. We set out to compare the frequencies of common SULT1A1 and SULT1A2 alleles in Caucasian, Chinese and African-American subjects. Allele frequencies for SULT1A1*1, *2 and 3 in 242 Caucasian subjects were 0.656, 0.332 and 0.012, respectively. Frequencies of those same alleles were significantly different in 290 Chinese subjects: 0.914, 0.080 and 0.006, respectively, as were frequencies in 70 African-American subjects: 0.477, 0.294 and 0.229, respectively. Ethnic variation in allele frequencies was also observed for SULT1A2, with frequencies in Caucasian subjects for SULT1A21, *2 and 3 of 0.507, 0.389 and 0.104; frequencies in Chinese of 0.924 and 0.076 with no 3 alleles observed; and, finally, in African-Americans frequencies of 0.637, 0.249 and 0.114, respectively. We also found that SULT1A12 and SULT1A22, the most common variant alleles for these two genes, were in positive linkage disequilibrium in all three populations studied, with D' values of 0.776 in Caucasian (P < 0.001), 0.915 in Chinese (P < 0.001) and 0.864 in African-American subjects (P < 0.001). These observations represent a step towards determining the possible functional implications for individual variations in sulfate conjugation of common genetic polymorphisms for SULT1A1 and SULT1A2.

摘要

磺基转移酶(SULT)催化药物、其他外源性物质、神经递质和激素的硫酸化结合反应。SULT1A1和SULT1A2的基因存在常见的基因多态性,这些多态性与酶活性水平的个体差异以及生化和物理性质的差异相关。我们着手比较白种人、中国人和非裔美国人中SULT1A1和SULT1A2常见等位基因的频率。242名白种人受试者中SULT1A11、2和3的等位基因频率分别为0.656、0.332和0.012。在290名中国受试者中,这些相同等位基因的频率显著不同,分别为0.914、0.080和0.006;在70名非裔美国受试者中,频率分别为0.477、0.294和0.229。在SULT1A2中也观察到等位基因频率的种族差异,白种人受试者中SULT1A21、2和3的频率分别为0.507、0.389和0.104;中国人中为0.924和0.076,未观察到3等位基因;最后,在非裔美国人中,频率分别为0.637、0.249和0.114。我们还发现,这两个基因最常见的变异等位基因SULT1A12和SULT1A2*2在所有三个研究人群中呈正连锁不平衡,在白种人中D'值为0.776(P < 0.001),在中国人为0.915(P < 0.001),在非裔美国受试者中为0.864(P < 0.001)。这些观察结果朝着确定SULT1A1和SULT1A2常见基因多态性对硫酸化结合个体差异可能的功能影响迈出了一步。

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