ABSTRACT
Previous studies have revealed that genetic factors may be involved in regulating folate turnover, e.g. methylenetetrahydrofolate reductase polymorphism in the development of male infertility. Folate transporter, encoded by the SLC19A1 gene, commonly referred to as reduced folate carrier (RFC) is a transmembrane protein, which transfers hydrophilic folates across the cell membrane. It was hypothesized that common polymorphism within the SLC19A1 gene (rs1051266:G>A, 80G>A) may alter RFC function. The aim of this study was to investigate a potential association between the SLC19A1 80G>A polymorphism and male infertility in a case-control study. The SLC19A1 80G>A polymorphism was determined by means of a polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) assay in 213 infertile Caucasian men and 226 ethnically matched controls. The distribution of SLC19A1 genotypes in the infertile men was as follows: GG 26.8%, GA 51.2%, AA 22.1% and in fertile men: GG 24.8%, GA 50.4%, AA 24.8%, and was comparable in the both the evaluated groups. Odds ratios (95% confidence interval, CI): 0.90 (0.59-1.38) and 0.88 (0.56-1.36) for dominant and recessive models remained non-significant, also after adjustment for age: 0.89 (0.57-1.37) and 0.80 (0.51-1.25), respectively. Our study demonstrated that polymorphism 80G>A of the SLC19A1 gene is not associated with male infertility.
Subject(s)
Infertility, Male/genetics , Membrane Transport Proteins/genetics , Polymorphism, Genetic , Adolescent , Adult , Age Factors , Case-Control Studies , Cell Membrane/metabolism , Genotype , Humans , Male , Middle Aged , Odds Ratio , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Reduced Folate Carrier ProteinABSTRACT
Infertility is a common problem affecting one in six couples, and in 30% of infertile couples, the male factor is a major cause due to defective sperm quality. P-glycoprotein (P-gp), a product of the MDR1 (ABCB1) gene, may be a link between genetic and environmental factors contributing to the development of male infertility because pesticides (P-gp substrates) are well established factors of male infertility. The aim of the present study was to examine the effect of the MDR1 gene 3435C>T polymorphism on male infertility. In total, 162 male patients undergoing semen analysis due to initial infertility workup were included in the study. The control group consisted of 191 healthy males with proven fertility. MDR1 3435C>T genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Assessment of MDR1 genotypes among the infertile men showed that 17.9% of subjects were carriers of the CC genotype, 58.0% were CT and 24.1% were TT. Among fertile men, 30.4% of subjects were characterised by the CC genotype, 49.7% were CT and 19.9% were TT. In addition, the frequency of carriers of at least one T allele (i.e., CT and TT genotypes) among infertile and fertile subjects was 82.1% and 69.6%, respectively. The risk of infertility was significantly elevated by two-fold in individuals carrying at least one T allele (CT and TT genotypes: p = 0.009, OR = 2.00, 95% CI: 1.20-3.32). Furthermore, this elevated risk was still found when considering each of the CT and TT genotypes alone (TT genotype: p = 0.027, OR = 2.05, 95% CI: 1.09-3.86; CT genotype: p = 0.013, OR = 1.98, 95% CI: 1.16-3.36). This preliminary report suggests that P-gp may play some role in male infertility, mediating detrimental effects of environmental factors.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Infertility, Male/genetics , Polymorphism, Single Nucleotide/genetics , Thymidine/genetics , ATP Binding Cassette Transporter, Subfamily B , Adult , Alleles , Genotype , Humans , Infertility, Male/diagnosis , Male , Middle Aged , Semen/physiology , Young AdultABSTRACT
In the last 50 years a significant decrease in human fertility has been observed. The result of research indicate that 6% of men aged 15-44 years are infertile or their fertility is significantly compromised. It has also been stated that 15% of couples have fertility problems. Among infertile couples it is a man who is responsible for 50% cases of infertility. Test results show that hormonal disturbances and abnormalities in semen production belong to main causes of infertility, while anatomic anomalie can be responsible for infertility only in few cases. Various chemical substances which appear in the environment may disturb fertility of men. Polluted soil, water and air are the sources of constant exposure to xenobiotics. Substances disturbing hormonal balance (endocrine disruptors) such as pesticide, dioxins and organic solvents cause the highest danger. Improper work conditions such as too high temperature, radiation, exposure to harmful substances also have negative influence on reproductive abilities of men. In addition, it has been noticed that both, some drugs and past infections of reproductive system may have a negative impact on fertility. Studies carried out in recent years have proven that improper lifestyle such as inadequate diet, alcohol abuse, smoking and long-term stress exposure can be the reason for fertility distrurbances in men. The latest findings have stressed genetic factors which may influence reproductive abilities of men.
