Association between polymorphisms of exon 12 and exon 24 of JHDM2A gene and male infertility

Background: Some dynamic changes occurs during spermatogenesis such as histone removal and its replacement with transition nuclear protein and protamine. These proteins are required for packing and condensation of sperm chromatin. JHDM2A is a histone demethylase that directly binds to promoter regions of Tnp1 and Prm1 genes and controls their expression by removing H3K9 at their promoters

Objective: The association between polymorphisms of exon 12 and exon 24 in JHDM2A gene and male infertility were evaluated for the first time

Materials and Methods: In this experimental study, 400 infertile men [oligospermia and azoospermia] and normal healthy fathers were evaluated [n=200]. Single Strand Conformation Polymorphism [SSCP-PCR] and polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] methods were used for screening any polymorphisms that are exist in exon 12 and exon 24

Results: Exon 24 PCR products were analyzed by RFLP but no polymorphism was found in this exon at the restriction site of EcoRV enzyme. Our monitoring along the whole nucleotides of exon 12 and exon 24 were continued using SSCP method, but we found no change along these exons

Conclusion: Generally, this study evaluated the association between polymorphisms in exon 12 and exon 24 of JHDM2A gene and male infertility which suggests that polymorphisms of these exons may not be associated with the risk of male infertility

Association between serum paraoxonase 1 activities [PONase/AREase] and L55M polymorphism in risk of female infertility

The risk of developing female infertility has been associated with gene polymorphisms that decrease the activity of enzymes involved in systemic Oxidative Stress [OS]. In this study, PON1 L55M polymorphism for association with susceptibility to infertility was investigated among Iranian female population. Samples from 120 Iranian females [20 endometriosis; 30 Polycystic Ovary Syndrome [PCO]; 70 controls] were analyzed and PCR-RFLP assay was used to determine the PON1 rs854560 [L55M] frequencies. The paraoxonase [PONase] and arilesterase [AREase] activities of PON1 enzyme were also assessed in order to investigate the association between serum PON1 activities, female infertility, and PON1 L55M polymorphism. The women with a MM genotype [p=0.021; OR=2.55] showed more possibilities of experiencing infertility than those with a LM genotype [p=0.039; OR=1.91]. According to LSD test, endometriosis subjects had significantly lower paraoxonase enzyme activity compared to control group [p=0.0024; CI=95%]. No significant difference was found in women with PCOS for both PONase and AREase activity in comparison with control group [p=0.469; CI=95%]. Furthermore, PON1 activities were the highest in LL genotype followed by LM and then MM genotype [MM

Multiplex PCR based screening for micro/partial deletions in the AZF region of Y-chromosome in severe oligozoospermic and azoospermic infertile men in Iran

Infertility is a health problem which affects about 10-20% of married couples. Male factor infertility is involved approximately 50% of infertile couples. Most of male infertility is regarding to deletions in the male-specific region of the Y chromosome. In this study, the occurrence of deletions in the AZF region and association between infertility and paternal age were investigated in Iranian men population. To assess the occurrence of Y chromosomal microdeletions and partial deletions of the AZF region, 100 infertile men and 100 controls with normal spermatogenesis were analyzed. AZFa, AZFb, AZFc and partial deletions within the AZFc region were analyzed using multiplex PCR method. Finally, the association between paternal age and male infertility was evaluated. No AZFa, AZFb or AZFc deletions were found in the control group. Seven infertile men had deletions as the following: one AZFb, five AZFc, and one AZFab. Partial deletions of AZFc [gr/gr] in 9 of the 100 infertile men [9/100, 9%] and 1 partial AZFc deletions [gr/gr] in the control group [1/100, 1%] were observed. In addition, five b2/b3 deletions in five azoospermic subjects [5/100, 5%] and 2 partial AZFc deletions [b2/b3] in the control group [2/100, 2%] were identified. Moreover, the risk of male infertility was influenced by the paternal age. The results of this study suggested that the frequency of Y chromosome AZF microdeletions increased in subjects with severe spermatogenic failure and gr/gr deletion associated with spermatogenic failure

New insights into VEGF-A alternative splicing: key regulatory switching in the pathological process

Vascular endothelial growth factor [VEGF-A] is one of the most important regulatory factors in pathological and physiological angiogenesis. Alternative splicing is a complicated molecular process in VEGF-A gene expression which adds complexity to VEGF-A biology. Among all VEGF-A exons, alternative splicing of exon 8 is the key determinant of isoform switching from pro-angiogenic VEGF-xxx to anti-angiogenic VEGF-xxxb. This is known as a key molecular switching in many pathological situations. In fact, the balance between VEGF-xxx and VEGF-xxxb isoforms is a critical controlling switch in both conditions of health and disease. Here, the properties of VEGF-xxx and VEGF-xxxb isoforms were discussed and their regulatory mechanism and their roles in certain pathological processes were evaluated. In summary, it was suggested that C-terminal VEGF-A alternative splicing can provide a new treatment opportunity in angiogenic diseases

Association between XPD [Lys751G1n] polymorphism and lung cancer risk: a population-based study in Iran

People are usually susceptible to carcinogenic aromatic amines, present in cigarrette smoke and polluted environment, which can cause DNA damage. Therefore, maintenance of genomic DNA integrity is a direct result of proper function of DNA repair enzymes. Polymorphic diversity could affect the function of repair enzymes and thus augment the risk of different cancers. Xeroderma pigmentosum group D [XPD] gene encodes one of the most prominent repair enzymes and the polymorphisms of this gene are thought to be of importance in lung cancer risk. This gene encodes the helicase, which is a component of transcription factor IIH and an important part of the nucleotide excision repair system. Studies reveal that individuals with Lys751Gln polymorphism of XPD gene have a low repairing capacity to delete the damages of ultraviolet light among other XPD polymorphisms. In this case-control study, first Lys751Gln polymorphism was genotyped, then its association with lung cancer risk was analyzed. Genomic DNA was extracted from the whole blood sample of 640 individuals from Iran [352 healthy individuals and 288 patients]. Allele frequencies and heterozygosity of Lys751Gln polymorphism were determined using polymerase chain reaction-restriction fragment length polymorphism method. According to statistical analyses, lung cancer risk in individuals with Lys751Gln polymorphism [Odd Ratio=1.8, 95% Confidence Interval 0.848-3.819] is approximately twice as high as that of Lys/Lys genotype, however 751Gln/Gln genotype did not relate to lung cancer risk [Odd Ratio=0.7, 95% Confidence Interval 0/307-1/595]. This study suggests that heterozygous polymorphism [Lys/Gln] increases the sensitivity of lung cancer risk, while homozygous polymorphism [Lys/Lys] probably decreases its risk and C allele frequency shows no remarkable increase in the patients

CYP1B1 L432V polymorphism and lung cancer risk in the Iranian population

Lung cancer is considered as one of the most frequent cancers worldwide, and has been the cause of more than one million mortalities each year. Exposure to tobacco smoke is the primary cause of most lung cancers, since it contains several thousand compounds, including more than 50 known carcinogens. However, a small fraction of individuals who are exposed to tobacco smoke develop lung cancer, therefore genetic factors may render some tobacco smokers more susceptible to cancer. Genetic polymorphism in genes that encode metabolizing enzymes may be related to differentiated susceptibility of malignancy. CYP1B1 protein is a member of the more significant CYP1 subfamily enzymes, involved in environmental carcinogen metabolic activation. The most studied polymorphism in CYP1B1 gene includes 4325 C-G, resulting in an amino acid change from leucine to valine amino acid. A case-control study [included 65 lung cancer cases and 80 healthy controls] was designed based on the RFLP-PCR method to estimate the possible association of this polymorphism with lung cancer susceptibility in the Iranian population. Regarding the distribution of CYP1B1 L432V genotypes, there were no meaningful differences among controls and lung cancer patients, however among patients carrying the CC genotype, tobacco smokers had a considerable elevated risk for lung cancer compared to those who had the GG genotype. CYP1B1 L432V polymorphism has an important role in lung cancer risk. Therefore, further studies are recommended for investigation of other related CYP1B1 gene polymorphisms, their association with affective genes and regulatory factors in the Iranian population.