Association of MDR1 C3435T and C1236T single nucleotide polymorphisms with male factor infertility

Abstract

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.

Role of MDR1 Gene Polymorphisms in Human Male Infertility: A Meta-Analysis

“…Infertility is undoubtedly a complicated pathological condition affecting 4% to 7% of the male population across the globe and is demonstrated as a broad range of heterogeneous phenotypes, from congenital or acquired urogenital abnormalities, endocrine disturbances, and immunological factors to spermatogenic quantitative and qualitative defects. It has been observed that 15% of infertile males have a genetic defect ( Aydos et al, 2015 ; Xavier et al, 2021 ).…”

“…The product of the MDR1 gene is P-glycoprotein, which is a probable link between the environmental and genetic factors that lead to the development of male infertility ( Droździk al., 2009 ). It has a shielding role and removes toxic substances such as xenobiotics from cells and prevents their buildup within cells, which serves as a protective measure for the organism ( Aydos et al, 2015 ). Xenobiotics, including pesticides, act as a substrate for P-glycoprotein.…”

“…P-glycoprotein influences the microenvironment of the seminiferous tubules by transporting testicular steroids. P-glycoprotein transfers a large number of xenobiotics including pesticides, which are well-known factors responsible for reducing male fertility ( Aydos et al, 2015 ).…”

Relationship of MDR1 gene polymorphism and P-glycoprotein expression in Chinese refractory lupus nephritis

“…The C1236T is a synonymous mutation that does not cause amino acid change (Kozhakhmetov et al 2013). While, C3435T is the only silent polymorphism currently identified, which may affect the expression of Pgp in different organs/tissues and even in different races (Aydos et al 2015).…”

Toxic metals and autism

“…but frequent polymorphisms (SNPs) that affect oxidative stress (GSTT1, GSTM1, SOD 2), and the detoxifying capacity (CYP2D6, CYP2C9, CYP2C19, NAT 2). [28,29] Clinically, this syndrome multifactorial and multisystemic, appears with a slowing of cognitive behavioral development (isolation, indifference, loss of contact with peers and family members) regression of the word, self behaviors and hetero aggressive and a long line of organic disorders, affecting intestinal function, immune and energy metabolism. [30] Since 1995 it is stated in the international arena the multidisciplinary approach for the prevention and treatment of developmental disorders (Defeat Autism Now, DAN!…”