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 reproductive functions in men might result from physiological, genetic, and/or environmental factors such as xenobiotics. The multi-drug resistance1 (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 xenobiotics. MDR1 is highly expressed at the luminal surface of capillary endothelial cells, and is expressed in Leydig cells, testicular macrophages, 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 models. 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. Further research in large cohorts with different populations is required to clarify the role of MDR in male fertility.
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 reproductive functions in men might result from physiological, genetic, and/or environmental factors such as xenobiotics. The multi-drug resistance1 (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 xenobiotics. MDR1 is highly expressed at the luminal surface of capillary endothelial cells, and is expressed in Leydig cells, testicular macrophages, 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 models. 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. Further research in large cohorts with different populations is required to clarify the role of MDR in male fertility.