CYP2C19°ú UGT1A1ÀÇ ½Å¼ÓÇÑ À¯ÀüÇü ºÐ¼®À» À§ÇÑ ÀÚµ¿È ÀåºñÀÇ Æò°¡
Evaluation of a Fully Automated, Rapid Detection System for CYP2C19 and UGT1A1 Genotyping
Laboratory Medicine and Quality Assurance 2014³â 36±Ç 2È£ p.92 ~ p.98
Àü¿ë¹ü(Jeon Yong-Bum) - ¼¿ï´ëÇб³º´¿ø Áø´Ü°Ë»çÀÇÇаú
À̽ÂÁØ(Lee Seung-Jun) - ¼¿ï´ëÇб³º´¿ø Áø´Ü°Ë»çÀÇÇаú
Á¶¼ºÀÓ(Cho Sung-Im) - ¼¿ï´ëÇб³º´¿ø Áø´Ü°Ë»çÀÇÇаú
¼¼öÇö(Seo Soo-Hyun) - ¼¿ï´ëÇб³º´¿ø Áø´Ü°Ë»çÀÇÇаú
³ªÀº°æ(Ra Eun-Kyung) - ¼¿ï´ëÇб³º´¿ø Áø´Ü°Ë»çÀÇÇаú
¹Ú½Â¸¸(Park Seung-Man) - °Ç±¹´ëÇб³º´¿ø Áø´Ü°Ë»çÀÇÇаú
¼º¹®¿ì(Seong Moon-Woo) - ¼¿ï´ëÇб³º´¿ø Áø´Ü°Ë»çÀÇÇаú
¹Ú¼º¼·(Park Sung-Sup) - ¼¿ï´ëÇб³º´¿ø Áø´Ü°Ë»çÀÇÇаú
Abstract
¹è°æ: ¾à¹°´ë»çÈ¿¼Ò¸¦ ¾ÏÈ£ÈÇÏ´Â À¯ÀüÀÚ¿¡¼ ´ÜÀÏ¿°±â´ÙÇü¼º(single nucleotide polymorphism, SNP)ÀÇ À¯ÀüÇü ºÐ¼®ÀÇ Çʿ伺Àº Áõ°¡ÇÏ°í ÀÖ´Ù. ±×·¯¹Ç·Î SNPÀÇ ½Å¼ÓÇÏ°í Á¤È®ÇÑ ÀÚµ¿È ºÐ¼®¹ýÀÌ ÃÖ±Ù ÁÖ¸ñ¹Þ°í ÀÖ´Ù.
¹æ¹ý: ÀúÀÚµéÀº 200¸íÀÇ Á¤»ó Çѱ¹ÀÎÀÇ DNA °Ëü¿Í 100¸íÀÇ ÀüÇ÷¿¡¼ i-densy IS-5310À» ÀÌ¿ëÇÑ ¼Ò±¤¼Ò½ÄÀÚ¹ý(quenching probe, QP)À¸·Î CYP2C19*2¿Í CYP2C19*3 À¯ÀüÀÚÀÇ À¯ÀüÇüÀ» ºÐ¼®Çß´Ù. ¶ÇÇÑ 200°³ÀÇ DNA¿Í 81°³ÀÇ ÀüÇ÷ °Ëü¿¡ ´ëÇØ UGT1A1*6¿Í UGT1A1*28 À¯ÀüÀÚÀÇ À¯ÀüÇüÀ» ºÐ¼®Çß´Ù. ºÐ¼®°á°ú´Â ÀüÅëÀû ¿°±â¼¿ºÐ¼®¹ý°ú ºñ±³µÇ¾ú´Ù.
°á°ú: CYP2C19ÀÇ ´ë¸³À¯ÀüÀÚ ºóµµ´Â *2¿¡ ´ëÇØ 25.7%, *3¿¡ ´ëÇØ 10.3%¿´À¸¸ç, UGT1A1¿¡¼´Â *6¿¡ ´ëÇØ 17.3%, *28¿¡ ´ëÇØ 11.2%·Î ±âÁ¸ÀÇ Çѱ¹Àο¡¼ÀÇ º¸°í¿Í À¯»çÇß´Ù. QP¹ý¿¡ ÀÇÇÑ CYP2C19 À¯ÀüÇüÀº Á÷Á¢¼¿ºÐ¼®¹ý°ú ¿Ïº®È÷ ÀÏÄ¡Çß´Ù(100.0%, K=1.000, P<0.001). 281°Ëü Áß, QP¹ý¿¡ ÀÇÇÑ UGT1A1 À¯ÀüÇüÀº ÇÑ °³ÀÇ °Ëü¸¦ Á¦¿ÜÇÏ°í ¿ª½Ã ÀÏÄ¡Çß´Ù(99.6%, K=0.992, P<0.001).
°á·Ð: QP¹ýÀº ±× °Ë»ç¼Óµµ¿Í »ç¿ë ¸é¿¡¼ ÀÓ»ó°Ë»ç½Ç¿¡¼ ºü¸£°í Á¤È®ÇÑ Áø´Ü¿¡ µµ¿òÀ» ÁÙ °ÍÀ¸·Î ÆǴܵȴÙ.
Background : The need for genotyping single nucleotide polymorphisms (SNPs) in genes encoding drug-metabolizing enzymes is increasing. Therefore, the recent focus has been on developing fully automated methods for the rapid and accurate measurement of SNPs. Methods: We used the quenching probe (QP) method and i-densy IS-5310 to genotype 200 DNA specimens from 200 healthy Koreans and 100 whole blood from another 100 for the SNPs CYP2C19*2 and CYP2C19*3. We also performed genotyping of UGT1A1*6 and UGT1A1*28 with the above mentioned 200 DNA samples and 81 whole blood samples. The results of the assay were then compared to conventional direct sequencing.
Method : We used the quenching probe (QP) method and i-densy IS-5310 to genotype 200 DNA specimens from 200 healthy Koreans and 100 whole blood from another 100 for the SNPs CYP2C19*2 and CYP2C19*3. We also performed genotyping of UGT1A1*6 and UGT1A1*28 with the above mentioned 200 DNA samples and 81 whole blood samples. The results of the assay were then compared to conventional direct sequencing.
Result : The allele frequencies of CYP2C19 were 25.7% for *2 and 10.3% for *3, and those of UGT1A1 were 17.3% for *6 and 11.2% for *28. These results are similar to those reported in previous studies on Korean populations. The CYP2C19 and UGT1A1 genotypes determined by the QP method perfectly matched (100.0%, ¥Ê=1.000, P<0.001 for CYP2C19, and 99.6%, ¥Ê=0.992, P<0.001 for UGT1A1) those determined by direct sequencing, barring a single exception for the UGT1A1 genotype in 1 DNA specimen.
Conclusion : Our results suggest that the QP method, owing to its speed and ease of use, will enable rapid and sensitive diagnosis in clinical laboratories.
Å°¿öµå
Genotyping, CYP2C19, UGT1A1, Single nucleotide polymorphism
KMID :
0985420140360020092
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