Association of CYP1A1 (cytochrome P450) MspI polymorphism in women with endometriosis.

Endometriosis is a disease that affects 10 to 15% of the women of reproductive age. It is characterized by the presence of endometrial-like tissues outside of the uterus. Some definitions claim that the functional ectopic tissue is sensitive to the action of hormones. Severity of endometriosis is defined according to a system proposed by the American Society for Reproductive Medicine, which is based on laparoscopic findings. A large number of genetic polymorphisms has been reported for CYP1A1, the gene that is responsible for enzymes involved in stage I detoxification of xenobiotics; this gene is located at 15q22-24, and encodes an isoenzyme that catalyzes the oxidation of polycyclic aromatic hydrocarbons present in phenolic compounds and epoxides. The aim of this study was to analyze the frequency of the MspI polymorphism and its relation to endometriosis. We obtained peripheral blood samples from 52 women with endometriosis (confirmed by laparoscopy) as well as 42 women without endometriosis (control group). In the case group, the women were between 25 and 35 years of age; the age range was between 25 and 57 years old in the control group. Molecular analysis was performed by polymerase chain reaction. We found a significant association (P = 0.039) between the polymorphic allele m1 and endometriosis (32.70%). In conclusion, this study showed that the m1 polymorphism is associated with endometriosis, and that W1/m1 and m1/m1 polymorphisms are more frequently observed in patients with infertility and severe endometriosis.

Association between RsaI polymorphism in estrogen receptor ß gene and male infertility.

The estrogen receptor ß (ERß) gene plays an important role in the regulation of fertility in both males and females. The RsaI polymorphism in ERß is associated with male infertility in Caucasian patients. The aim of this study was to investigate the frequency of this polymorphism in the etiology of idiopathic male infertility and its correlation with smoking habits. We analyzed 287 Brazilian men, including 161 infertile and 126 fertile men, to evaluate the association between the RsaI polymorphism and male infertility. The RsaI variant alleles of all patients were determined by allele-specific polymerase chain reaction. Compared with a control group (normozoospermic men), the frequency of the RsaI AG-genotype was four times higher in infertile men (P = 0.01), five times higher in azoospermic men (P = 0.02), and seven times higher in teratozoospermic men (P = 0.001). The frequency of the RsaI AG-genotype was three times higher in infertile smokers (P = 0.038) compared with infertile nonsmokers, and nine times higher in azoospermic smokers (P = 0.035) compared with azoospermic nonsmokers. The RsaI polymorphism in ERß may have modulating effects on human spermatogenesis. There seems to be a consistent association between RsaI polymorphism and smoking habits in infertile men.

GSTM1 and GSTT1 polymorphisms in endometriosis in women from Goiás, Brazil.

Endometriosis is a gynecologic pathology with a high prevalence and unknown etiology. Therefore, an increasing number of studies has been undertaken to search for associations between endometriosis and alterations or polymorphisms in candidate genes, including glutathione S-transferase mu 1 (GSTM1) and glutathione S-transferase theta 1 (GSTT1). We analyzed the frequency of present/absent polymorphisms of GSTM1 and GSTT1 in 50 women diagnosed with endometriosis and in a control group of 46 women without complaints related to this pathology. The association of these polymorphisms with p53 gene codon 72 was also evaluated within each group, and a higher frequency of absence of GSTM1 (61%) and GSTT1 (45%) genes in the group of women studied, women with endometriosis and control group was found. The contributions of GSTM1 and GSTT1 polymorphisms to the proliferation of endometriosis were not statistically significant, but the analysis of pathology and the association of GSTM1 and GSTT1 gene polymorphisms with p53 codon 72 revealed statistical significance.

Polymorphism of the progesterone receptor gene associated with endometriosis in patients from Goiás, Brazil.

We investigated a possible link between endometriosis and polymorphism of the progesterone receptor gene (PROGINS). The endometriosis group consisted of 54 patients with a diagnosis of endometriosis by laparoscopy, and the control group comprised 44 women without endometriosis. Genotypes for PROGINS polymorphisms (A1/A1, A1/A2 and A2/A2) were determined by polymerase chain reaction and analyzed on a 2% agarose gel stained with ethidium bromide. The frequency of polymorphic genotypes (A1/A2 and A2/A2) was significantly higher in patients with endometriosis (33%) than in the control group (16%). We conclude that there is a significant correlation between PROGINS polymorphism and endometriosis.

RsaI polymorphism of the ERß gene in women with endometriosis.

We examined the frequency of RsaI polymorphism of the ERß gene in 54 patients diagnosed with endometriosis and 46 controls. Peripheral blood was collected from women undergoing laparoscopy with a confirmed diagnosis of endometriosis. Polymorphisms of the ERß gene and p53 were assessed by PCR and analyzed on 2% agarose gel stained with ethidium bromide. The AG polymorphism genotype frequency in patients with endometriosis was 59.3%, with 40.7% GG. In the control group, the frequency of AG was 6.5%, with 93.5% GG. The frequency of heterozygous AG was nine times higher in patients with endometriosis than in the control group (P < 0.0001).

Glutathione S-transferase M1 and T1 polymorphism in men with idiopathic infertility.

Male infertility is a heterogeneous disorder, with various genetic and environmental factors that contribute to the impairment of spermatogenesis. Genetic causes are responsible for 60% of cases of idiopathic infertility. Polymorphisms of genes that encode detoxifying enzymes of phase II drug metabolism can modify their expression or function, affecting the biotransformation of toxic compounds to which the male reproductive system is exposed. GSTM1 and GSTT1 encode enzymes that are essential in the process of detoxification of endogenous and exogenous xenobiotics, facilitating their excretion. We examined GSTM1 and GSTT1 polymorphism in 233 men with idiopathic infertility seen at the Human Reproduction Service of the Federal University of Goiás from 2004-2006. Genotype GSTM1/T1 (null) was found in 30/105 normal individuals and in 64/128 abnormal individuals, indicating a significant association with idiopathic male infertility. The sperm alteration associated with greater GSTM1/T1 (null) frequency was decreased sperm count (oligozoospermy), which was more frequent in patients with GSTM1 (78.9%) as well as in those who had GSTT1 (73.7%), although the difference was not significant. Individuals polymorphic for genes GSTM1 and GSTT1 are susceptible to reduction in sperm quality and infertility, possibly because oligozoo spermic individuals have been affected by GST polymorphism.

Y chromosome microdeletions in Brazilian fertility clinic patients.

Microdeletions in Yq are associated with defects in spermatogenesis, while those in the AZF region are considered critical for germ cell development. We examined microdeletions in the Y chromosomes of patients attended at the Laboratory of Human Reproduction of the Clinical Hospital of the Federal University of Goiás as part of a screening of patients who plan to undergo assisted reproduction. Analysis was made of the AZF region of the Y chromosome in men who had altered spermograms to detect possible microdeletions in Yq. Twenty-three patients with azoospermia and 40 with severe oligozoospermia were analyzed by PCR for the detection of six sequence-tagged sites: sY84 and sY86 for AZFa, sY127 and sY134 for AZFb, and sY254 and sY255 for AZFc. Microdeletions were detected in 28 patients, including 10 azoospermics and 18 severe oligozoospermics. The patients with azoospermia had 43.4% of their microdeletions in the AZFa region, 8.6% in the AZFb region and 17.4% in the AZFc region. In the severe oligozoospermics, 40% were in the AZFa region, 5% in the AZFb region and 5% in the AZFc region. We conclude that microdeletions can be the cause of idiopathic male infertility, supporting conclusions from previous studies.

Y chromosome microdeletions in Brazilian fertility clinic patients

Microdeletions in Yq are associated with defects in spermatogenesis, while those in the AZF region are considered critical for germ cell development. We examined microdeletions in the Y chromosomes of patients attended at the Laboratory of Human Reproduction of the Clinical Hospital of the Federal University of Goiás as part of a screening of patients who plan to undergo assisted reproduction. Analysis was made of the AZF region of the Y chromosome in men who had altered spermograms to detect possible microdeletions in Yq. Twenty-three patients with azoospermia and 40 with severe oligozoospermia were analyzed by PCR for the detection of six sequence-tagged sites: sY84 and sY86 for AZFa, sY127 and sY134 for AZFb, and sY254 and sY255 for AZFc. Microdeletions were detected in 28 patients, including 10 azoospermics and 18 severe oligozoospermics. The patients with azoospermia had 43.4% of their microdeletions in the AZFa region, 8.6% in the AZFb region and 17.4% in the AZFc region. In the severe oligozoospermics, 40% were in the AZFa region, 5% in the AZFb region and 5% in the AZFc region. We conclude that microdeletions can be the cause of idiopathic male infertility, supporting conclusions from previous studies.