ITPKC基因功能性SNPrs28493229与中国人群川崎病的相关性研究  

Association study of a functional SNP rs28493229 of 1TPKC gene and Kawasaki disease in a Chinese population

作　　者：彭茜[1] 陈昌辉[1] 吴青[1] 李波[1] 廖静[1] 罗彩丹[1] 胡小平[1] 郑植[1] 何海兰[1] 张渝[1] 

机构地区：[1]四川省人民医院儿科,成都610072

出　　处：《中华医学遗传学杂志》2011年第6期644-648,共5页Chinese Journal of Medical Genetics

摘　　要：目的分析中国人群中1，4，5三磷酸肌醇3激酶C基因（inositol1，4，5-trisphosphate3kinaseC，ITPKc）功能性单核苷酸多态位点（singlenucleotidepolymorphism，SNP）rs28493229（G／C）与川崎病（Kawasakidisease，KD）临床表型的相关性。方法进行病例对照研究，实验组包括206例KD患儿，对照组包含年龄与性别相近的285名非KD婴幼儿。采用聚合酶链反应－限制性片段长度多态性与DNA测序两种技术对研究对象的ITPKC基因的rs28493229多态进行分型，比较实验组与对照组、实验组中继发与不继发冠状动脉损伤（coronaryarterylesions，CALs）、以及静脉注射免疫球蛋白（intravenousimmunoglobulin，IVIG）治疗敏感与不敏感病例中rs28493229等位基因与基因型的频率。结果实验组与对照组rs28493229的C等位基因频率均显著低于日本人群（P〈0．01）。该SNP等位基因、基因型与C等位基因携带者频率在实验组与对照组、继发与不继发CALs患者组以及IVIG治疗敏感与不敏感患者组之间均未发现统计学差异。结论ITPKC基因rs28493229多态与中国人群川崎病的发生和发展不存在显著的相关性，提示该SNP的C等位基因不能作为判断中国人群川崎病易患性、患者预后及疗效的分子遗传标记。相较于日本人群，中国人群中rs28493229显著偏低的c等位基因频率，可能会削弱其在该人群KD／CALS发病中的重要性。进一步对ITPKC基因内其它多态位点的研究，不排除发现中国人群中与KD／CALS发生密切相关的功能性SNP的可能。Objective Kawasaki disease （KD） is a form of acute multi-systemic vasculitis with unknown etiology. It is the leading cause of acquired heart disease in children due to the frequent occurrence of coronary artery lesions （CALs）. Recently, a C allele of rs28493229 （G/C） in inositol 1, 4, 5- trisphosphate 3-kinase C （ITPKC） gene was found to significantly increase the risk for KD/CALs in Japanese population. It is important to confirm such finding in Chinese population to enable prognosis and personalized therapy for KD. Methods A case-control study was performed. The patient group has included 206 unrelated patients with KD, and the control group included 285 age, gender and ethnically matched children who never had KD. Genotyping of rs28493229 was performed using polymerase chain reaction restriction fragment length polymorphism（PCR RFLP） and DNA sequencing. The allele, genotype and C allele carrier frequencies were compared between the two groups, patients with or without CALs, and patients who were resistant or responsive to （intravenous immunoglobulin, IVIG） treatment. Results Frequency of the C allele of rs28493229 was significantly lower in both groups than that in the Japanese population （P.〈~0.01）. No significant difference was detected between the two groups in terms of allele, genotype and C carrier of rs28493229 frequencies. Such frequencies were also similar between patients with or without CALs, resistant or responsive to IVIG treatment. Conclusion Our study has failed to prove any association between rs28493229 and KD/CALs in Chinese patients, which indicated that the C allele of rs28493229 may not be used as a molecular marker for determining KD susceptibility, prognosis and effect of treatment. The much lower frequency of C allele does not support its significance in the occurrence of KD/ CALs in Chinese population. It is still necessary to find functional SNPs in ITPKC gene which is associated with KD/CALs in Chinese population.

关 键 词：川崎病 冠状动脉损伤 1  4  5三磷酸肌醇3激酶C基因 单核苷酸多态性 

分 类 号：R725.4[医药卫生—儿科]