Interdisciplinary School of Health Sciences, University of Pune, Pune, India.
Indian J Med Res. 2011 Mar;133(3):274-9.
BACKGROUND & OBJECTIVES: Many pharmacologically-relevant polymorphisms show variability among different populations. Though limited, data from Caucasian subjects have reported several single nucleotide polymorphism (SNPs) in folate biosynthetic pathway. These SNPs may be subjected to racial and ethnic differences. We carried out a study to determine the allelic frequencies of these SNPs in an Indian ethnic population.
Whole blood samples were withdrawn from 144 unrelated healthy subjects from west India. DNA was extracted and genotyping was performed using PCR-RFLP and Real-time Taqman allelic discrimination for 12 polymorphisms in 9 genes of folate-methotrexate (MTX) metabolism.
Allele frequencies were obtained for MTHFR 677T (10%) and 1298 C (30%), TS 3UTR 0bp (46%), MDR1 3435T and 1236T (62%), RFC1 80A (57%), GGH 401T (61%), MS 2756G (34%), ATIC 347G (52%) and SHMT1 1420T (80%) in healthy subjects (frequency of underlined SNPs were different from published study data of European and African populations).
INTERPRETATION & CONCLUSIONS: The current study describes the distribution of folate biosynthetic pathway SNPs in healthy Indians and validates the previous finding of differences due to race and ethnicity. Our results pave way to study the pharmacogenomics of MTX in the Indian population.
许多与药理学相关的多态性在不同人群中存在差异。尽管数据有限，但来自白种人群体的研究报告了叶酸生物合成途径中的几个单核苷酸多态性（SNP）。这些 SNP 可能存在种族和民族差异。我们进行了一项研究，以确定这些 SNP 在印度人群中的等位基因频率。
从印度西部的 144 名无关健康受试者中抽取全血样本。提取 DNA 后，使用 PCR-RFLP 和实时 Taqman 等位基因鉴别法对叶酸-甲氨蝶呤（MTX）代谢中 9 个基因的 12 个多态性进行基因分型。
获得了 MTHFR 677T（10%）和 1298C（30%）、TS 3'UTR 0bp（46%）、MDR1 3435T 和 1236T（62%）、RFC1 80A（57%）、GGH 401T（61%）、MS 2756G（34%）、ATIC 347G（52%）和 SHMT1 1420T（80%）在健康受试者中的等位基因频率（下划线 SNP 的频率与欧洲和非洲人群的已发表研究数据不同）。
本研究描述了叶酸生物合成途径 SNP 在健康印度人中的分布，并验证了由于种族和民族差异的先前发现。我们的研究结果为研究 MTX 在印度人群中的药物基因组学铺平了道路。
