Prevalence of chromosome defects in azoospermic and oligoastheno-teratozoospermic South Indian infertile men attending an infertility clinic.

The prevalence of chromosomal abnormalities in azoospermic and oligoastheno-teratozoospermic infertile men of South Indian origin undergoing assisted reproductive technologies was evaluated. In addition, the study aimed to investigate new abnormal karyotypes involving autosomes in azoospermia and sex chromosomes in oligoastheno-teratozoospermic individuals that are supposed to be rare. Metaphase chromosomes of 744 infertile men, including 272 men with azoospermia and 472 men with oligoastheno-teratozoospermia (OAT), were analysed using Giemsa-trypsin-Giemsa banding and fluorescence in-situ hybridization (FISH) wherever necessary. Chromosomal abnormalities were observed in 59 (7.9%) individuals of the total studied population. Among these, 30 out of 272 (11.0%) azoospermic men and 29 out of 472 (6.1%) infertile men with OAT showed chromosomal abnormalities. A strong and statistically significant association (OR = 1.89; P = 0.0235) of chromosomal abnormalities and sex chromosome abnormalities (OR = 4.29; P = 0.001) with azoospermia when compared with OAT was observed. In addition, six autosomal abnormalities associated with azoospermia and two abnormalities involving Y chromosome, which include a novel karyotype (mos 46,XY/51,XYYYYYY) in OAT individuals, were detected.

GSTM1, GSTT1 and CYP1A1 detoxification gene polymorphisms and their relationship with advanced stages of endometriosis in South Indian women.

OBJECTIVE(S): Studies on association between endometriosis and various phase I and phase II detoxification genes such as glutathione S-transferase M1 and theta 1 (GSTM1 and GSTT1) and cytochrome P450 (CYP1A1) have produced inconsistent results possibly because of ethnic differences. The present study was undertaken to investigate the frequency of the CYP1A1 (6235T>C) polymorphism and GSTM1, GSTT1 null mutations in a South Indian women's population with and without endometriosis. METHODS: The frequencies of variants were studied in 310 women with laparoscopically proven endometriosis (rAFS III=101; IV=209) and 215 women without endometriosis using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The GSTM1 null deletion showed significant association (P=0.028) with endometriosis. No significant difference was found in the frequencies of the GSTT1 null deletion in cases and controls. The frequencies of the variant CYP1A1 homozygous and heterozygous alleles in the cases were 9% and 44.2% against 14.4% and 42.3% in the controls. Further, we observed a considerable difference in the GSTM1 null deletion frequency in this population when compared with other populations of the world. CONCLUSIONS: We observed an association between endometriosis and the GSTM1 null deletion, but not with GSTT1 null deletions or the CYP1A1 MspI polymorphism in South Indian women.

N-acetyl transferase 2 polymorphism and advanced stages of endometriosis in South Indian women.

Aylamine-N-acetyl transferase is a phase II detoxification enzyme encoded by the gene NAT2. Single nucleotide polymorphism (SNP) changes from the wild type NAT2 *4 allele result in allelic variants *5, *6 and *7. Homozygotes for the NAT2 *4 wild type are fast acetylators; heterozygotes with one wild-type allele and a variant NAT2 *5, *6 or *7 allele have reduced enzyme activity and individuals with two variant alleles are slow acetylators. Previous studies have implicated NAT2 as a susceptibility factor in endometriosis. This study investigated the NAT2 allele frequencies and genotype distributions in 252 unrelated women with endometriosis and 264 controls of South Indian origin. No differences were found between the frequencies of fast and slow acetylators in cases (34.9% and 65.1%) and controls (33.3% and 66.7%). Two NAT2 genotypes *7/*7 (1.2%) and *5/*6/*7 (1.6%) were detected in endometriosis cases only. Four new combinations, 6D (481 + 590 mutation), 7C (590 + 857), 7D (590 + 803 + 857) and 7E (481 + 590 + 803 + 857) were detected, which have not been reported earlier. Similar genotype and phenotype results were obtained in 33 affected sister-pairs. The case-control data from this study suggest there is no association between endometriosis and NAT2 in South Indian women; however, two new variant genotypes and seven SNP combinations were also identified in cases only, which suggests that the gene may still have some as yet undetermined role in the disease.

CYP1A1, GSTM1 and GSTT1 genetic polymorphism is associated with susceptibility to polycystic ovaries in South Indian women.

Polymorphic variants in the phase I enzyme, cytochrome P450 gene, may lead to increased toxification, whereas polymorphisms in the phase II enzyme, glutathione S-transferase genes, may result in impaired detoxification. Alterations in the activities of phase I drug metabolizing enzymes and phase II detoxification enzymes may cause abnormal functioning and formation of follicular cysts in the ovaries and thus causing an imbalance in the hormone profiles. This study aimed to investigate the relationship between genetic polymorphisms of CYP1A1 (T6235C), GSTM1 and GSTT1 in South Indian women with polycystic ovaries (PCO) using polymerase chain reaction-restriction fragment length polymorphism. The frequencies of variants of these genes were studied in 180 women with confirmed PCO and in 72 healthy fertile women with successful pregnancy record. No significant difference was found between the frequencies of GSTM1 and GSTT1 null genotypes in PCO cases and healthy controls. However, CYP1A1 Msp I homozygous mutants were strongly associated (P = 0.0139) with increased susceptibility to PCO. Three genotype combinations, CYP1A1 (mt/mt) with GSTM1 [-] and GSTT1 [-], CYP1A1 (wt/mt) with GSTM1 [-] and GSTT1 [-] and CYP1A1 (mt/mt) with GSTM1 [-], GSTT1 [+], were also observed in women with PCO. In conclusion, the presence of hyperinducible CYP1A1 (T6235C) mutant genotype and its mutants in combination with GSTM1 and GSTT1 null genotypes might cause an imbalance between phase I and phase II enzymes, and therefore may represent a risk factor for PCO.