No Association between DNA Repair Gene (XPD, XRCC1, and XRCC4) Polymorphisms and Nonsyndromic Microtia in Turkish Patients

Abstract

Sir: Microtia is defined as a malformation of the auricle, ranging from minimal abnormalities to major structural alterations or even total absence of the external ear. The incidence of microtia is reported to vary from 0.83 to 17.4 per 10,000 births.1 XRCC1 (x-ray cross-complementing group 1 protein) is involved in the repair of DNA base damage and single-strand DNA breaks.2 The XPD (xeroderma pigmentosum group D) protein is an essential 5′-3′ helicase involved in the nucleotide excision repair pathway, and in regulation of transcription, the cell cycle, and apoptosis.3 X-ray repair cross-complementing group 4 (XRCC4) gene's protein functions together with DNA ligase IV and the DNA-dependent protein kinase in the repair of DNA double-strand break.4 The aim of this study was to investigate the links between DNA repair enzyme (XPD, XRCC, and XRCC4) variants and nonsyndromic microtia. Nineteen nonsyndromic microtia patients and 40 healthy controls were included in this study. We studied the polymorphisms of XPD (751), XRCC1 (-399), and XRCC4 (-1394 and variable number of tandem repeat in intron 3) genes. The study was approved by the local ethical committee, and informed consent was obtained from the patients. A chi-square test was used for statistical analysis of genotype and allele frequencies in the case and control groups. Hardy-Weinberg equilibrium was calculated using the de Finetti program. The distribution of GG, GA, and AA genotypes for XRCC1 (-399) polymorphism was 21, 31.5, and 47.5 percent (p = 0.161) in cases compared with 30, 32.5, and 37,5 percent in the controls (p = 0.028), respectively. The distribution of AA, AC, and CC genotypes for XPD (-751) polymorphism was 52.6, 26.3, and 21.1 percent in cases (p = 0.07) compared with 52.5, 14, and 5 percent in the controls (p = 0.291), respectively. The distribution of II, ID, and DD genotypes for XRCC4 variable number of tandem repeat polymorphism was 47.4, 26.3, and 26.3 percent in cases (p = 0.05) compared with 25, 60, and 15 percent in the controls (p = 0.179), respectively. Also, the distribution of TT, GT, and GG genotypes for XRCC4 (-1394) polymorphism was 52.6, 31.6, and 15.8 percent in cases (p = 0.24) compared with 37.5, 37.5, and 25 percent in the controls (p = 0.132), respectively (Table 1).Table 1: Analyzed DNA Repair Genes and Their Genotype Distributions in Patients and Control GroupsXPD, XRCC1, and XRCC4 are all genes involved in the DNA repair process. They are responsible for regulation of apoptosis and proliferation during development. Our aim was to investigate a possible association between the polymorphisms of these genes and nonsyndromic microtia. The statistical analysis of genotype and allele frequencies of case and control groups did not turn out to be statistically meaningful. DNA repair gene polymorphisms and their linkage to nonsyndromic microtia were not studied hitherto. Although no association was found between DNA repair gene polymorphisms and nonsyndromic microtia, designing such an experiment with a much larger patient group would yield more accurate results. For further studies, candidate genes that have a predominant cartilage expression and major impact on apoptosis and cell proliferation during development are good options. Tugce Sever, M.Sc.Bio. Department of Medical Biology and Genetics Berker Buyukgural, M.D. Department of Plastic and Reconstructive Surgery Sacide Pehlivan, Ph.D. R. Ozgur Rosti, M.D. Department of Medical Biology and Genetics Mehmet Bekerecioglu, M.D. Department of Plastic and Reconstructive Surgery Gaziantep University Faculty of Medicine Gaziantep, Turkey