Genetic Polymorphisms in Pakistani Women With Polycystic Ovary Syndrome

Abstract

Polycystic ovary syndrome (PCOS) is the major cause of anovulatory infertility. Although the genetic basis of PCOS is not well understood, it is a common metabolic and endocrine disorder. This study investigates the possible genomic variants associated with PCOS in Pakistani women from the Punjab region. DNA samples from 96 patients with genetically unrelated PCOS and 96 controls were analyzed by direct sequencing to determine the polymorphisms of different loci on follicle-stimulating hormone receptor (fshr), follicle-stimulating hormone β (fshrβ), luteinizing hormone chorionic gonadotropin (lhcgr), luteinizing hormone β (lhβ), estrogen receptor α (esr1), and estrogen receptor β (esr2) genes. Significant associations were observed within the genotype frequencies, allele frequencies, and multi-single-nucleotide polymorphism (SNP) haplotype analysis of most polymorphisms studied. This study identified new SNPs at positions 605+52 Del/T in lhcgr genes occurring in this particular subpopulation. The strong r (2) value suggests that polymorphisms in the fshr and esr1 genes were in linkage disequilibrium. Our study provides evidence of statistically significant associations between susceptibility to PCOS in Pakistani women and the gene polymorphisms mentioned earlier. This suggests that the susceptible loci for PCOS lie within or very close to the chromosomal regions spanning these genes.

Variant Alleles of the ESR1, PPARG, HMGA2, and MTHFR Genes Are Associated With Polycystic Ovary Syndrome Risk in a Chinese Population: A Case-Control Study

“…Conversely, the GA genotype of rs1999805 in ESR1 , and the TT genotype of rs1801133 in MTHFR were significantly associated with increased risk of PCOS. Associations of ESR1 rs9340799 (25), HMGA2 rs2272046 (21), and MTHFR rs1801133 (32) with PCOS risk have been reported in other studies. In contrast, our results appear to provide the first evidence linking rs1999805 in ESR1 and rs709154 in PPARG with PCOS risk in a Chinese population.…”

“…Whatever the underlying mechanism, the association between ESR1 polymorphism and risk of PCOS appears to depend in complex ways on ethnicity. A Pakistani study linked the CC genotype of ESR1 rs2234693, the GG genotype of rs9340799, and the CT genotype of rs8179176 with elevated disease risk (25). However, studies in Greeks (34) and Caucasians (35) revealed no differences in frequencies of these genotypes between PCOS patients and controls.…”

“…For example, FSHR rs6166 was associated with increased PCOS risk in a study of 377 Chinese PCOS patients and 388 age-matched healthy controls (23), but not in a study in a different ethnic population (24). ESR1 rs9340799 has been associated with increased PCOS risk in a Pakistani population (25), but not in a Brazilian population (26). …”

Molecular Characterization and Expression Profiles of the Ovine LHβ Gene and Its Association with Litter Size in Chinese Indigenous Small-Tailed Han Sheep

“…Previous studies related to LHβ gene polymorphisms have focused mainly on human reproductive disorders [24,25]. Basavarajappa et al identified seven different variants of the LHβ gene in the Indian river buffalo (Bubalus bubalis) based on a polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis [26].…”

Association between Luteinizing Hormone/Choriogonadotropin Receptor Ins18LQ Gene Polymorphism and Polycystic Ovary Syndrome

“…The study on genes susceptible to PCOS has focused mainly on gene polymorphisms that encode sex hormones and regulatory proteins such as folliclestimulating hormone ß, follicle-stimulating hormone receptor, luteinizing hormone/choriogonadotropin receptor (LHCGR), estrogen receptor alphareceptor (ESR1), and estrogen receptor ß (ESR2). Variants of genetic markers have implications for the predisposition of PCOS; however, there are no variants that are directly and repeatedly linked to PCOS [3], [6].…”