title: Association of MDR1 C3435T and C1236T single nucleotide polymorphisms with male factor infertility.
abstract: Infertility affects 1 in 6 couples and approximately 1 in 25 men. Male factor infertility is a major cause of spermatogenic anomalies, the causes of which are largely unknown. Impaired repro-ductive functions in men might result from physiological, genetic, and/or environmental factors such as xenobiotics. The multi-drug re-sistance1 (MDR1) gene encodes a P-glycoprotein which has a role in the active transport of various substrates providing protection of somatic cells from potentially toxic substances, including xenobi-otics. MDR1 is highly expressed at the luminal surface of capillary endothelial cells, and is expressed in Leydig cells, testicular mac-rophages, and Sertoli cells. We performed genotype and haplotype analyses of MDR1 in 192 infertile and 102 fertile Turkish men for the genetic markers C1236T and C3435T, using polymerase chain reaction-restriction fragment length polymorphism analysis. In the overall population, correlations were analyzed in all genotype mod-els. We found that the C3435T polymorphism TT vs CT genotypes showed statistically significant differences in their association with infertility (P = 0.045), and that the CT genotype was associated with high sperm DNA damage (P = 0.02), suggesting that the CT genotype might be a susceptibility factor for infertility. Additionally, the T-T haplotype was significantly more frequent in the control group (13.2 vs 6.5%; odds ratio = 0.459, 95%CI = 0.259-0.814, P = 0.006). This study showed that MDR1 might have a role in male infertility. Fur-ther research in large cohorts with different populations is required to clarify the role of MDR in male fertility.
authors.affiliation: Department of Medical Biology, School of Medicine, Ankara University, Ankara, Turkey saydos@gmail.com.
authors.forename: S E
authors.initials: SE
authors.lastname: Aydos
authors.affiliation: Department of Medical Biology, School of Medicine, Ankara University, Ankara, Turkey.
authors.forename: A
authors.initials: A
authors.lastname: Karadağ
authors.affiliation: Department of Medical Biology, School of Medicine, Ankara University, Ankara, Turkey.
authors.forename: T
authors.initials: T
authors.lastname: Özkan
authors.affiliation: Vocational School of Health, Medical Laboratory Techniques, Ankara University, Ankara, Turkey.
authors.forename: B
authors.initials: B
authors.lastname: Altınok
authors.affiliation: Department of Medical Biology, School of Medicine, Ankara University, Ankara, Turkey.
authors.forename: M
authors.initials: M
authors.lastname: Bunsuz
authors.affiliation: Department of Medical Biology, School of Medicine, Ankara University, Ankara, Turkey.
authors.forename: S
authors.initials: S
authors.lastname: Heidargholizadeh
authors.affiliation: Reproductive Health Research Center, School of Medicine, Ankara University, Ankara, Turkey.
authors.forename: K
authors.initials: K
authors.lastname: Aydos
authors.affiliation: Department of Medical Biology, School of Medicine, Ankara University, Ankara, Turkey.
authors.forename: A
authors.initials: A
authors.lastname: Sunguroğlu
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000328:Adult; D000483:Alleles; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007248:Infertility, Male / Q000235:genetics* / Q000473:pathology; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014421:Turkey
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B