Screening for variants in the <i>MUTYH</i>gene in Saudis

作     者：Jameela Shinwari Abdulla Alamri Mohammad Alanazi Nada Al Tassan 

作者机构：Department of Biochemistry Genome Research Chair College of Science King Saud University 

出 版 物：《Open Journal of Genetics》 (遗传学期刊（英文）)

年 卷 期：2011年第1卷第3期

页      面：70-77页

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

主　　题：MUTYH Allele Frequencies Single Nucleotide Polymorphism Mutations Colorectal Cancer 

摘      要：MUTYH is a base excision repair glycosylase responsible for correcting the G:A mismatches that arise from replication of a damaged DNA, such impairment results from attacks by reactive oxygen species that are produced from different sources including cigarette smoking. The produced reactive oxygen species trigger the oxidation of guanine in to 8-oxo-G and the latter mispairs with adenine. Alterations in the MUTYH gene can affect its glycosylase function and hence the DNA repair capacity that is tightly linked to cancer development. Defects in the MUTYH were found to be associated with predisposition to colorectal cancer;the third most common cancer in the world. Although some studies suggested the existence of an ethnic differentiation among MUTYH mutations, there are no documented reports regarding this gene in Saudi cases or controls so far. 153 healthy Saudi individuals including smokers were screened for the IVS1 + 5 G/C, V22M, Y165C, R231C, H324Q and G382D MUTYH variants using either ARMS or RFLP or direct sequencing. Allelic frequencies were calculated and were found to be as follows: IVS1 + 5 G/C = 1/0, V22M = 0.99/0.01, Y165C = 1/0, R231C = 1/0, H324Q = 0.29/0.71 and G382D = 0.997/0.003. Comparison of the allele frequencies between Saudis and other populations revealed a significant difference between the Saudis and Europeans for the V22M (p-value: 0.0003, OR: 5.899, 95% CI: 1.999 - 17.408);and between the Saudis and Asians for the H324Q (p-value: MUTYH variants in Saudi populations and support the existence of an ethnic difference between MUTYH variants which is beneficial as some MUTYH common polymorphisms in certain populations may correlate with disease predisposition in other rare populations.