Screening for genetic variants of MUTYH gene in a random sample from Riyadh

Abstract

MUTYH is one of the base excision repair glycosylases that are particularly responsible for correcting the G: A mismatches arising from replication of a damaged DNA, such damage is produced from attacks by reactive oxygen species. These reactive substances can be produced from different sources including cigarette smoking, and they basically oxidize Guanine to 8-oxo-G that is able to mispaire 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. Recently it has been proven that defects in the MUTYH are associated with predisposition to colorectal cancer; the third most common cancer in the world. On the other Abstract :(do not increase about 700 Word) hand an ethnic differentiation among MUTYH mutations has been suggested, such difference can affect susceptibility to colorectal cancer and possibly treatment outcomes. The data available to date regarding the MUTYH variants are almost entirely performed in the western populations, therefore, it is of an essential importance to determine the MUTYH allele frequencies in Saudis and compare them with other populations. In this study, DNA was extracted from the blood of 153 healthy Saudi individuals including smokers, the MUTYH gene was amplified then screened for the IVS1+5 G/C, V22M, Y165C, R231C, H324Q and G382D MUTYH variants using different methods. The mutant V22M allele was detected in a few heterozygous subjects, while the mutant G382D mutation was detected in a single heterozygous sample. As for the common polymorphism H324Q, 50% of the subjects were homozygous for the mutant allele, 40% samples were heterozygous and less than 10% samples were homozygous for the wild type allele. As for IVS1+5 G/C, Y165C and R231C only the normal alleles were present and no mutant alleles were detected in the sample studied. These data allowed the construction of Using the 5 different haplotypes for the Saudi samples. proper statistical program, the allele frequency for each variant was calculated and compared between smokers and non-smokers, and between Saudis and other populations. The comparison revealed a statistical significant difference between the Saudis and Europeans V22M allele frequency; also it revealed a significant difference between the Saudis and Asians H324Q allele frequency. Comparison between smokers and nonsmokers did not result in any significant difference for all the six variants. Further analysis for the MUTYH mutations in Saudi colorectal cancer patients and in other types of cancers would help in a better understanding of these diseases and their treatment.