Rattanacheeworn Punyabhorn, Chamnanphon Monpat, Thongthip Siriwan, Kittanamongkolchai Wonngarm, Townamchai Natavudh, Avihingsanon Yingyos, Udomnilobol Udomsak, Prueksaritanont Thomayant, Jianmongkol Suree, Chariyavilaskul Pajaree
Clinical Pharmacokinetics and Pharmacogenomics Research Unit, Chulalongkorn University, Bangkok, Thailand.
Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Pharmgenomics Pers Med. 2020 Oct 22;13:521-530. doi: 10.2147/PGPM.S268457. eCollection 2020.
Genetic polymorphisms of drug transporters influence drug transporter activity and alter pharmacokinetic profiles of the drugs. Organic anion transporting polypeptide 1B1 (OATP1B1) and breast cancer resistance protein (BCRP) are important transporters encoded by solute carrier organic anion transporter family member 1B1 () gene and ATP-binding cassette subfamily G member 2 () gene, respectively. Polymorphisms in these genes are associated with increased plasma statins concentrations, statin-induced myopathy and poor response to allopurinol treatment.
We explored allele and genotype frequencies of S and genes including their predicted phenotypes in 53 Thai participants. Of these, 17 had chronic kidney disease and were on statins.
Genotyping analysis for c.521T>C (rs4149056), c.388A>G (rs2306283), g.-11187G>A (rs4149015), and c.421C>A (rs2231142) was done by using TaqMan Real time PCR. All were tested for Hardy-Weinberg Equilibrium.
Most of the participants (80%) had normal function haplotypes ( and ) while decreased ( and ) and unknown () function haplotypes were less observed. Four phenotypes of were observed: 69.81% had normal function (,, and ), 13.21% had intermediate function (, and ), 9.43% had indeterminate function ( and ) and 7.55% had low function ( and ). c.421A allele frequency was 25%. The frequency of c.421CA and AA phenotypes were 37.7% and 5.7%, respectively. The allele and genotype frequencies observed are consistent with reports in Asians. However, there were differences in major allele distributions between Asians and Caucasians for c.388A>G; c.388G were highly found in Asians, but c.388A were more observed in Caucasians.
This study showed that in the Thai population, there were 4 SNPs of and genes. This finding may be clinically applied to minimize inter-individual variability of drugs such as statins and allopurinol. Further study with a larger sample size is needed to assess the drug profiles and responses to treatment.
药物转运体的基因多态性会影响药物转运体活性，并改变药物的药代动力学特征。有机阴离子转运多肽1B1（OATP1B1）和乳腺癌耐药蛋白（BCRP）分别是由溶质载体有机阴离子转运体家族成员1B1（SLCO1B1）基因和ATP结合盒亚家族G成员2（ABCG2）基因编码的重要转运体。这些基因的多态性与他汀类药物血浆浓度升高、他汀类药物诱导的肌病以及对别嘌醇治疗反应不佳有关。
我们在53名泰国参与者中探究了SLCO1B1和ABCG2基因的等位基因和基因型频率，包括其预测的表型。其中，17人患有慢性肾脏病且正在服用他汀类药物。
采用TaqMan实时荧光定量PCR对SLCO1B1基因的c.521T>C（rs4149056）、c.388A>G（rs2306283）、g.-11187G>A（rs4149015）以及ABCG2基因的c.421C>A（rs2231142）进行基因分型分析。所有样本均进行哈迪-温伯格平衡检验。
大多数参与者（80%）具有正常功能的单倍型（H1和H3），而功能降低（H2和H4）和功能未知（Hx）的单倍型较少见。观察到SLCO1B1的四种表型：69.81%具有正常功能（H1、H3、H5和H6），13.21%具有中等功能（H7、H8和H9），9.43%具有不确定功能（H10和H11），7.55%具有低功能（H12和H13）。ABCG2基因c.421A等位基因频率为25%。ABCG2基因c.421CA和AA表型的频率分别为37.7%和5.7%。观察到的等位基因和基因型频率与亚洲人群的报道一致。然而，对于SLCO1B1基因的c.388A>G，亚洲人和白种人的主要等位基因分布存在差异；c.388G在亚洲人中高度常见，但c.388A在白种人中更常见。
本研究表明，在泰国人群中，SLCO1B1和ABCG2基因存在4个单核苷酸多态性。这一发现可能在临床上用于最小化他汀类药物和别嘌醇等药物的个体间变异性。需要进一步开展更大样本量的研究来评估药物特征和治疗反应。
