Copy number variation in sulfotransferase isoform 1A1 (SULT1A1) is significantly associated with enzymatic activity in Japanese subjects.
Copy number variation in sulfotransferase isoform 1A1 (SULT1A1) is significantly associated with enzymatic activity in Japanese subjects.
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DOI：
10.2147/pgpm.s36579
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发表时间：
2013
影响因子：
1.9
通讯作者：
Kadlubar S
中科院分区：
文献类型：
--
作者：
Yu X;Kubota T;Dhakal I;Hasegawa S;Williams S;Ozawa S;Kadlubar S
磺基转移酶亚型 1A1 (SULT1A1) 在多种内生素和外生素的代谢中发挥着关键作用，其活性可能影响对药物的反应。我们之前的研究重点是 SULT1A1 基因变异对白种人和非裔美国人酶活性的影响。然而，遗传变异对亚洲人 SULT1A1 活性的影响尚未被探索。在这项研究中，我们研究了日本受试者中 SULT1A1 拷贝数变异 (CNV) 和启动子区、编码区和 3' 非翻译区的单核苷酸多态性 (SNP) 对 SULT1A1 活性的集体影响。 SULT1A1 启动子和 3' 非翻译区中的 SNP 与 SULT1A1 活性无关（P > 0.05）。 SULT1A1*1/2 (Arg213His) 与 SULT1A1 活性略有相关 (P = 0.037)。然而，SULT1A1 CNV 与 SULT1A1 活性密切相关（趋势检验 P = 0.008），占日本受试者观察到的活性变异的 10%。总之，SULT1A1 CNV 在日本受试者 SULT1A1 活性测定中发挥着关键作用，凸显了 SULT1A1 基因变异的种族差异对药物代谢和治疗效果的影响。
Sulfotransferase isoform 1A1 (SULT1A1) plays a key role in the metabolism of a variety of endo- and xenobiotics and it’s activity could influence response to drugs. Our previous studies have focused on the impact of genetic variants of SULT1A1 on enzymatic activity in Caucasians and African-Americans. However, the contribution of genetic variants to SULT1A1 activity in Asians has not been explored. In this study, we investigated the collective effects of both SULT1A1 copy number variants (CNVs) and single nucleotide polymorphisms (SNPs) in the promoter region, coding region, and 3′ untranslated region on SULT1A1 activity in Japanese subjects. SNPs in the SULT1A1 promoter and 3′ untranslated region were not associated with SULT1A1 activity (P > 0.05). SULT1A1*1/2 (Arg213His) was marginally associated with SULT1A1 activity (P = 0.037). However, SULT1A1 CNVs were strongly associated with SULT1A1 activity (trend test P = 0.008) and accounted for 10% of the observed variability in activity for Japanese subjects. In conclusion, SULT1A1 CNVs play a pivotal role in determination of SULT1A1 activity in Japanese subjects, highlighting the influence of ethnic differences in SULT1A1 genetic variants on drug metabolism and therapeutic efficacy.