Gyoung Hoon Lee

Follicle-stimulating hormone receptor gene polymorphism and ovarian responses to controlled ovarian hyperstimulation for IVF-ET

AbstractThis study was performed to investigate the association between FSH receptor (FSHR) gene polymorphism at position 680 and the outcomes of controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer (IVF-ET) in Korean women. Two hundred and sixty-three patients under 40 years of age who underwent IVF-ET procedures were included in this study. Patients with polycystic ovary syndrome, endometriosis, or a previous history of ovarian surgery were excluded. Following extraction of genomic DNA, the FSHR polymorphism at position 680 was determined by polymerase chain reaction and restriction fragment length polymorphism analysis. The FSHR genotype distribution was 41.8% for Asn/Asn, 45.6% for Asn/Ser, and 12.5% for Ser/Ser FSHR genotype groups. Although there was no difference among the three genotype groups in terms of the age and infertility diagnosis of study subjects, the basal levels of FSH (day 3) were significantly different [5.7 ± 0.3 IU/l (mean±SEM), 6.0 ± 0.3 IU/l, and 8.2 ± 0.9 IU/l for Asn/Asn, Asn/Ser, and Ser/Ser groups, respectively. The Ser/Ser group tended to require a higher dose of gonadotropins for COH, and tended to show lower serum estradiol levels at the time of hCG administration than the other two groups, though these differences did not reach statistical significance. The numbers of oocytes retrieved tended to be different for the three groups (9.6 ± 0.6, 10.2 ± 0.6, and 7.9 ± 0.8 for Asn/Asn, Asn/Ser, and Ser/Ser groups, respectively). Clinical pregnancy rate was significantly higher in Asn/Asn, compared to the others (45.7 vs. 30.5%, P=0.013). The homozygous Ser/Ser genotype of FSHR polymorphism at position 680 may be associated with a reduced ovarian response to COH for IVF-ET, while Asn/Asn genotypes showed a higher pregnancy rate.

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.

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

Association of Peroxisome Proliferator-Activated Receptor-Gamma 2 Pro12Ala Polymorphism with Advanced-Stage Endometriosis

Citation Hwang KR, Choi YM, Kim JM, Lee GH, Kim JJ, Chae SJ, Moon SY. Association of peroxisome proliferator‐activated receptor‐gamma 2 Pro12Ala polymorphism with advanced‐stage endometriosis. Am J Reprod Immunol 2010

Interleukin-2 receptor β gene C627T polymorphism in Korean women with endometriosis: a case–control study

BACKGROUND The purpose of this study was to investigate the potential association of the C627T polymorphism in the interleukin-2 receptor beta gene (IL-2R beta) with the risk of endometriosis in Korean women. METHODS Two hundred and thirty-seven women with surgically or histologically diagnosed endometriosis of stages III and IV were recruited for this study, and 164 patients with no evidence of endometriosis diagnosed by laparoscopy or laparotomy served as controls. The C627T polymorphism of the IL-2R beta was assessed using the TaqMan allelic discrimination assay. Chi2 analysis was used to examine any differences in genotype distributions and allele frequencies of the IL-2R beta C627T polymorphism between the endometriosis cases and the controls. RESULTS There was no statistically significant difference in the frequency of the IL-2R beta C627T polymorphism between the endometriosis patients and the controls (28.7% C/C, 48.1% C/T and 23.2% T/T versus 29.3, 44.5 and 26.2%, respectively, P = 0.72) or in the T allele frequencies (47.3 versus 48.5%, respectively, P = 0.73). Even when the endometriosis cases were subdivided into stages III and IV, no statistically significant differences in genotype distributions or allele frequencies were observed among the three groups. CONCLUSIONS Contrary to the recent data reported in a Taiwanese population, our results suggest that the C627T polymorphism of the IL-2R beta gene may not be associated with the risk of endometriosis in the Korean population.

Association of CDKN2B-AS and WNT4 genetic polymorphisms in Korean patients with endometriosis.

OBJECTIVE To investigate whether specific genetic polymorphisms in the cyclin-dependent kinase inhibitor 2B antisense RNA (CDKN2B-AS) gene and near the wingless-type MMTV integration site family member 4 (WNT4) gene are associated with endometriosis in a Korean population. DESIGN Case-control genetic association study. SETTING University. PATIENT(S) Surgically or histologically diagnosed cases of endometriosis (n=673) and controls (n=500) among a population of ethnic Koreans. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Genotype distribution and synergistic interaction. RESULT(S) Significant differences were found in the allele distributions of the CC genotype of the rs10965235 single-nucleotide polymorphism (SNP) of the CDKN2B-AS gene and the GG genotype of the rs16826658 SNP on chromosome 1p36 between the endometriosis cases and the controls (rs10965235: 69.7% CC, 26.9% CA, and 3.4% AA vs. 59.2% CC, 35.2% CA, and 5.6% AA; rs16826658: 33.7% GG, 48.4% GT, and 17.8% TT vs. 25.6% GG, 49.8% GT, and 24.6% TT, respectively). A significant interaction was not found between the CC genotype of the rs10965235 SNP and the GG genotype of the rs16826658 SNP after Bonferroni correction (32.8% of CC+GG and 67.2% of CC+non-GG in the endometriosis cases vs. 25.0% of CC+GG and 75.0% of CC+non-GG in the controls). CONCLUSION(S) Our results suggest that the rs10965235 SNP in the CDKN2B-AS gene and the rs16826658 SNP near the WNT4 gene were significantly associated with endometriosis in this Korean population.

Association of epidermal growth factor receptor gene polymorphisms with advanced endometriosis in a Korean population

OBJECTIVES To determine if specific single nucleotide polymorphisms (SNPs) in the Epidermal Growth Factor Receptor (EGFR) gene were meaningful markers for the risk of advanced stage endometriosis in a Korean population. STUDY DESIGN Case-control study in a collective of 299 women with endometriosis and 285 controls. Three polymorphisms (151904 A>T [T628T] on exon 16 [rs 17337023], 162093 G>A [Q787Q] on exon 20 [rs 10251977], and 181946 C>T [D994D] on exon 25 [rs 2293347]) were assessed by a Minor Groove Binder (MGB) primer/probe Taqman assay. In-silico haplotypes were deduced using the Haploview (version 3.32) software package. RESULTS There were no statistically significant differences in the genotype or haplotype frequencies of the three EGFR polymorphisms between subjects with endometriosis versus the control group. Even when the endometriosis cases were subdivided into stage III and IV based on the ASRM criteria, no statistically significant differences in genotype distribution or haplotype frequencies were observed between the three groups. CONCLUSIONS Our results suggest that the 151904 A>T, 162093 G>A, and 181946 C>T polymorphisms in the EGFR gene are not associated with advanced stage endometriosis in a Korean population. Our results are in agreement with the results reported by Inagaki et al.