Aynur Karadag

Impact of follicle-stimulating hormone receptor variants in female infertility

PurposeFollicle-stimulating hormone (FSH) and its receptor play a major role in the development of follicles and regulation of steroidogenesis in the ovary and spermatogenesis in the testis. We aim to analyze the role of FSHR gene variants (single nucleotide polymorphisms (SNPs) in exon 10 (codon 307 and 680) and in the core promoter region (at position −29) and Ala189Val inactivating mutation) in Turkish infertile women. There were studies analyzing the effects of the SNPs in exon 10 (codon 307 and 680) and in the core promoter region (at position −29) of the FSHR gene on spermatogenesis, but to our knowledge, there were no studies analyzing the effects of these three SNP combinations on female fertility.MethodsIn this study, the allelic, genotype, and haplotype frequency distributions of these three SNPs in the FSHR gene were analyzed in 102 infertile women and 99 unrelated healthy control individuals. The distribution of the polymorphisms was conformed by Hardy–Weinberg equilibrium test.ResultsThere were no statistical differences (P > 0.05) in the allele, genotype, and haplotype frequencies of the polymorphisms and FSH, luteinizing hormone (LH), estradiol (E2), and prolactin (PRL) levels between the infertile patients and the controls. However, a significant relation was found between 307 SNP GA genotype and FSH level ≥12. We did not find any homozygous or heterozygote mutations in infertile patients and healthy fertile controls.ConclusionThe present study was the first study analyzing gma mutation and the polymorphism of the FSHR core promoter at position −29 alone and in combination with the two common SNPs in exon 10 in Turkish infertile women population. These findings indicate the significance of Ala307Thr GA genotype may be a predictive marker for poor ovarian reserve and infertility.

MDR1 gene polymorphisms may be associated with Behçet's disease and its colchicum treatment response

Behçets disease (BD) is a chronic multisystem disorder. Infectious agents, immune system mechanisms, and genetic factors are implicated in the etiopathogenesis of BD, which remains to be explained. The human MDR1 (ABCB1) gene encoder P-glycoprotein (P-gp) plays a key role in drug disposition, serves as a protective mechanism against xenobiotics, and provides additional protection for the brain, testis, and fetus. We investigated the genotype and haplotype distributions of three MDR1 gene polymorphisms (C1236T, G2677T/A, and C3435T) in 104 BD patients and 130 control subjects. The genotyping analysis was performed by using PCR-RFLP methods. No statistically significant differences were found for the genotypic and allelic distributions of three individual single nucleotide polymorphisms (SNPs) in the MDR1 gene between BD patients and control subjects in this study (p>0.05). However, combined genotype and haplotype frequencies have found statistically significant differences between BD and control subjects for some combinations (p<0.05). The CC-GG binary genotype for C1236T-G2677T/A loci couple in particular may have a high degree of predisposition to BD (p=0.009; OR, 3.03; 95% CI, 1.41-6.54). Furthermore, significant differences between colchicine-responsive and -nonresponsive groups were found. Genotypic and allelic distributions of C3435T and G2677T/A loci, as well as their genotype and haplotype combinations, were found to have statistically significant differences (p<0.05). The TT genotype for the C3435T locus (p=0.001; OR, 6.59; 95% CI, 1.86-23.30) and T allele (p=0.009; OR, 2.09; 95% CI, 1.18-3.70) plays a substantial role in the colchicine response. Our study showed that MDR1 genes and their polymorphisms may affect a patients BD susceptibility and colchicine response.

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

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.