Min A. Hong

Estrogen receptor α gene polymorphisms in patients with idiopathic premature ovarian failure

BACKGROUND It has been reported that polymorphisms in the estrogen receptor (ER)-alpha gene (ESR1) may be associated with reproductive patterns of women. This study was performed to investigate whether the genetic polymorphisms of the ER-alpha gene are associated with idiopathic premature ovarian failure (POF) in a Korean population. METHODS The subjects were 126 idiopathic POF patients and 221 post-menopausal controls recruited from university hospitals between 1999 and 2004. Genotyping was performed by MGB primer/probe Taqman assay. Haplotypes were deduced by using the Haploview version 4.1. Bonferroni correction was applied for the correction of multiple testing. RESULTS There was no significant difference in the allele distribution of the ER-alpha gene (TA)n repeats between the POF and the control group. For the PvuII polymorphism, the POF group showed a higher frequency of TT genotype compared with the controls (41.3 versus 26.3%, P = 0.004, 98.75% CI 1.8-28.2%). No significant difference was found in the distribution of the XbaI polymorphism between the POF and the control group. Haplotype analysis showed that the frequency of TA haplotype was significantly higher in the POF patients compared with the controls (64.7 versus 52.7%, P = 0.002, 98.75% CI 2.4-21.6%). CONCLUSIONS These findings suggest that the ER-alpha gene polymorphisms may be associated with idiopathic POF.

Association of tumor necrosis factor-α gene polymorphisms with advanced stage endometriosis

BACKGROUND This study was performed to investigate whether specific haplotypes and several single nucleotide polymorphisms in the promoter region of the tumor necrosis factor (TNF)-alpha gene are associated with the risk of advanced stage endometriosis in a Korean population. METHODS This study comprised women with (n = 246) or without (n = 248) endometriosis. The TNF:g.[-1031T > C], TNF:g.[-863C > A] and TNF:g.[-857C > T] polymorphism in the TNF-alpha gene were assessed by PCR-restriction fragment length polymorphism analysis, which utilized digestion by BbsI, HypCH4IV and HypCH4IV restriction enzymes, respectively. In silico haplotypes were deduced by using the Haploview version 3.32. RESULTS The genotype distribution of TNF:g.[-1031T > C] was significantly different between total endometriosis patients and the controls (T/T of 56.9 versus 60.1%, T/C of 35.4 versus 37.5% and C/C of 7.7 versus 2.4%, respectively, P = 0.027). This difference at the TNF:g.[-1031T > C] tends to increase in Stage IV endometriosis (P = 0.01). However, there was no difference in the TNF:g.[-863C > A] and TNF:g.[-857C > T] site between the two groups. Even when the endometriosis cases were subdivided into American Society for Reproductive Medicine Stages III and IV, genotype differences were not found. The CC homozygote at TNF:g.-863 was more frequently found in the controls than Non-CC group (P = 0.04; odds ratio = 0.67; 95% confidence interval = 0.45-0.98). All haplotypes and diplotypes, deduced by in silico analysis, showed no association with subgroups or controls. CONCLUSIONS Our results suggest that the genotype frequencies at the TNF:g.[-1031T > C] and the TNF:g.[-863C > A] sites may be associated with advanced stage endometriosis in the Korean population.

Polycystic ovary syndrome is not associated with polymorphisms of the TCF7L2, CDKAL1, HHEX, KCNJ11, FTO and SLC30A8 genes

Insulin resistance is a core feature of polycystic ovary syndrome (PCOS). Recently, genome‐wide association studies have reported a number of single‐nucleotide polymorphisms (SNPs) with reproducible associations and susceptibilities to type 2 diabetes. We examined the potential association between the diabetogenic genes uncovered in the genome‐wide association studies and PCOS in Korean women.

X chromosome inactivation patterns in patients with idiopathic premature ovarian failure

BACKGROUND X chromosome aberrations have been reported as the cause of extremely skewed X chromosome inactivation (XCI). The purpose of this study was to investigate whether skewed XCI is associated with idiopathic premature ovarian failure (POF). METHODS The XCI status was evaluated in Korean women by the methylation assay of androgen receptor locus in 126 idiopathic POF patients (35.3 +/- 13.9 years old, mean +/- SD) and 126 age-matched controls (35.2 +/- 13.9 years). The incidence of skewed XCI in POF group was compared with that of control. The correlation between age and skewed XCI was also evaluated within both groups. RESULTS The incidence of extremely skewed XCI (>or=90%) was 3.9 versus 2.7% (P = 0.710) in POF and control group, respectively. No significant differences were found in the incidence of skewed XCI on all three levels (>or=90, >or=80 and >or=70%) compared between these two groups. The calculation of correlation coefficients showed that, in both POF and control group, there were no significant correlations between age and XCI ratio. Neither was there increasing tendency of skewed XCI according to the increase of age in both groups. Furthermore, there were no significant differences when the XCI ratios were analysed according to the age of onset of ovarian failure. CONCLUSIONS The incidence of skewed XCI in Korean POF population was not significantly different from control, implying that skewed XCI may not be associated with idiopathic POF. There were also no significant correlations between age and skewed X-inactivation patterns in both groups.

The PAI-1 4G/5G and ACE I/D Polymorphisms and Risk of Recurrent Pregnancy Loss: A Case–Control Study

Thrombophilia has been postulated to be a contributor to the pathophysiology of recurrent pregnancy loss (RPL). We investigated the role of the plasminogen activator inhibitor type 1 (PAI‐1) 4G/5G and angiotensin converting enzyme (ACE) I/D polymorphisms in Korean patients with RPL.

Inhibin α gene promoter polymorphisms in Korean women with idiopathic premature ovarian failure

BACKGROUND It has been suggested that variations in the inhibin α gene (INHA) may affect the ovarian function of women. This study was performed to investigate whether the genetic polymorphisms of the INHA gene are associated with idiopathic premature ovarian failure (POF) in a Korean population. METHODS The subjects consisted of 159 idiopathic POF patients and 233 post-menopausal controls. Genotyping for the -16C>T polymorphism was performed by an minor groove binder (MGB) primer/probe Taqman assay, and the -124A>G polymorphism was identified using PCR restriction fragment length polymorphism analysis. Haplotypes were deduced by using the Haploview version 4.1. RESULTS There were no significant differences in the genotype distributions or allele frequencies of the INHA gene -16C>T and -124A>G polymorphisms between the POF and the control group. Haplotype analysis also showed no significant difference between groups. CONCLUSIONS The distribution of the INHA gene promoter polymorphisms in a Korean POF population was not significantly different from controls, implying that the INHA gene polymorphisms may not be associated with the risk of idiopathic POF.

No association between the GSTP1 exon 5 polymorphism and susceptibility to advanced stage endometriosis in the Korean population.

CitationJeon MJ, Choi YM, Hong MA, Lee GH, Ku SY, Kim SH, Kim JG, Moon SY. No Association between the GSTP1 exon 5 polymorphism and susceptibility to advanced stage endometriosis in the Korean population. Am J Reprod Immunol 2010; 63: 222–226

ORIGINAL ARTICLE: No Association Between the GSTP1 Exon 5 Polymorphism and Susceptibility to Advanced Stage Endometriosis in the Korean Population

CitationJeon MJ, Choi YM, Hong MA, Lee GH, Ku SY, Kim SH, Kim JG, Moon SY. No Association between the GSTP1 exon 5 polymorphism and susceptibility to advanced stage endometriosis in the Korean population. Am J Reprod Immunol 2010; 63: 222–226

Intercellular Adhesion Molecule-1 and Interleukin-6 Gene Polymorphisms in Patients with Advanced-Stage Endometriosis

Background/Aims: The aim of this study was to investigate the possibility that the K469E and G241R polymorphisms in the intercellular adhesion molecule-1 (ICAM-1) gene and the C-634G polymorphism in the interleukin (IL)-6 gene are associated with endometriosis in the Korean population. Methods: The ICAM-1 gene K469E and G241R polymorphisms and the IL-6 gene C-634G polymorphism were evaluated in 390 patients with endometriosis and 351 controls by polymerase chain reaction-restriction fragment length polymorphism analysis. Results: The ICAM-1 gene G241R polymorphism was not observed in all subjects. No differences were observed in the ICAM-1 K469E and IL-6 C-634G genotype distributions and allele frequencies between patients with endometriosis and controls. In subgroup analyses according to the stage of endometriosis or bilaterality of ovarian endometriomas, no significant differences were observed in the ICAM-1 gene K469E or the IL-6 gene C-634G polymorphism frequencies between the subgroups and the controls. The combined analysis of the ICAM-1 gene K469E polymorphism and the IL-6 gene C-634G polymorphism did not show any additional significant findings. Conclusions: The K469E and G241R polymorphisms in the ICAM-1 gene and the C-634G polymorphism in the IL-6 gene may not be genetic factors related to susceptibility to advanced-stage endometriosis in the Korean population.

Phosphatidylinositol 3-kinase p85α regulatory subunit gene Met326Ile polymorphism in women with polycystic ovary syndrome

BACKGROUND Insulin resistance is a core feature of polycystic ovary syndrome (PCOS). Phosphatidylinositol (PI) 3-kinase is an important enzyme in the early insulin signaling cascade and plays a key role in insulin-mediated glucose transport. In its regulatory subunit, p85alpha, there is a common amino acid substitution (the Met326Ile polymorphism), and this amino acid may be crucial for the function of the p85alpha regulatory subunit and PI3-kinase. METHODS Analysis of the Met326Ile polymorphism was carried out on DNA samples from 256 PCOS patients and 283 controls. Clinical and biochemical profiles of participants were also compared. RESULTS The genotype distribution of the Met326Ile polymorphism in the PCOS group was not different from that of the controls (Met326Met/Met326Ile/Ile326Ile rates were 73.4%/23.4%/3.2% and 70.3%/26.1%/3.6% for the PCOS and control groups, respectively, P = 0.72). The PCOS group was divided into two subgroups according to the presence of the variant 326Ile allele. Compared with those carrying at least one variant 326Ile allele, carriers with the Met326Met genotype had higher serum 17-hydroxyprogesterone (17-OHP) {1.1 [95% confidence interval (CI) 1.1-1.3] ng/ml in those with the Met326Met genotype versus 0.8 (95% CI 0.7-1.0) ng/ml in those with Ile326Ile and Met326Ile genotypes, P = 0.0073} and free testosterone levels [1.2 (95% CI 1.1-1.4) pg/ml for Met326Met genotype versus 0.9 (95% CI 0.6-1.3) pg/ml for Ile326Ile and Met326Ile genotypes, P = 0.038]. CONCLUSIONS Our results suggest that the PI3-kinase gene Met326Ile polymorphism may not be a major determinant for the development of PCOS, but it may modulate the concentrations of serum 17-OHP or free testosterone in PCOS patients.