Department of Pharmacology and Pharmacogenomics Research Center, Inje University College of Medicine, Inje University, Busan, South Korea.
Drug Metab Pharmacokinet. 2013;28(4):372-7. doi: 10.2133/dmpk.dmpk-12-sc-110. Epub 2013 Jan 29.
SULT1A1 and SULT1A2 are encoded on the same chromatid, and exhibit a 96% amino acid similarity. To screen for genetic variants in these two closely related genes, SULT1A1 and SULT1A2 were directly sequenced in 50 healthy Koreans. A total of 30 variations were identified in SULT1A1: eight in exons, thirteen in introns, and nine in the 5'-untranslated region. With regard to SULT1A2, 21 variants were identified, comprising seven in exons, five in introns, and nine in the 5'-untranslated region. Among these 51 variations, one in SULT1A1 and eight in SULT1A2 were previously unidentified, which include three coding variants (SULT1A2 R37Q, 110G>A; SULT1A2 G50S, 148G>A; SULT1A2 F286L, 3819C>A) and one null allele (SULT1A2 E217Stop, 3542G>T). Two LD blocks, major haplotype structures, and 7 haplotype-tagging SNPs were determined together for SULT1A1 and SULT1A2 as a single set. Frequencies of common functional variants were compared among ethnic groups. Since these two SULT enzymes are on the same chromatid in a parallel direction with overlapping substrate specificities, a combined analysis using LD and haplotype-tagging single-nucleotide polymorphisms (SNPs) will facilitate understanding of the variations in the sulfation reactions of a wide range of substrates, as compared with analysis of individual genes.
SULT1A1 和 SULT1A2 编码在同一染色单体上，具有 96%的氨基酸相似性。为了筛选这两个密切相关基因中的遗传变异，对 50 名韩国健康个体的 SULT1A1 和 SULT1A2 进行了直接测序。在 SULT1A1 中共发现了 30 个变异，其中 8 个位于外显子，13 个位于内含子，9 个位于 5'非翻译区。对于 SULT1A2，共发现了 21 个变体，其中 7 个位于外显子，5 个位于内含子，9 个位于 5'非翻译区。在这 51 个变异中，有 1 个在 SULT1A1 中，8 个在 SULT1A2 中，之前未被识别，包括 3 个编码变异（SULT1A2 R37Q，110G>A；SULT1A2 G50S，148G>A；SULT1A2 F286L，3819C>A）和 1 个无效等位基因（SULT1A2 E217Stop，3542G>T）。确定了 SULT1A1 和 SULT1A2 作为一个整体的 2 个 LD 块、主要单倍型结构和 7 个单倍型标记 SNP。比较了不同种族群体中常见功能变异的频率。由于这两种 SULT 酶在同一染色单体上以平行方向排列，具有重叠的底物特异性，因此使用 LD 和单倍型标记 SNP 的联合分析将有助于理解广泛底物的磺化反应中的变异，而不是分析单个基因。
