The effects of luteinising hormone gene polymorphism on the outcomes of in vitro fertilisation and embryo transfer.

Trp8Arg polymorphism of the LH beta gene has decreased bioactivity in vivo and previous studies showed conflicting data on the effect of LH beta gene polymorphism on the IVF outcome. In this study, 591 IVF patients were recruited. Patients with the variant allele(s) were the carrier group. In GnRH antagonist cycles, the clinical pregnancy rate was significantly lower in the carrier group (18.9%) than in the noncarrier group (37.1%). In long GnRH agonist cycles, the clinical pregnancy rate was comparable between both groups. To clarify the effect of COH protocols, IVF outcomes in the GnRH antagonist and long GnRH agonist protocol groups in carriers were analysed. Among carriers, the clinical pregnancy rate was significantly lower in the GnRH antagonist protocol group (18.9%) than in the long GnRH agonist protocol group (45.2%). Single nucleotide polymorphism analysis may contribute to the individualisation of COH protocols for each patient in the future.Impact StatementWhat is already known on this subject? Trp8Arg polymorphism of the LH beta gene is known to have decreased bioactivity in vivo. Previous studies have demonstrated hypo-sensitivity in the patients with the variant LH beta protein, while other study showed similar carrier frequency between the poor and the normal response group.What the results of this study add? The variant LH beta gene was associated with a lower clinical pregnancy rate in GnRH antagonist cycles but not in long GnRH agonist cycles.What the implications are of these findings for clinical practice and/or further research? Single nucleotide polymorphism analysis may contribute to the individualisation of COH protocols for each patient in the future.

Association Between Polycystic Ovary Syndrome and the Polymorphisms of Aryl Hydrocarbon Receptor Repressor, Glutathione-S-transferase T1, and Glutathione-S-transferase M1 Genes.

OBJECTIVE: To investigate the association between the aryl hydrocarbon receptor repressor (AhRR) C/G polymorphisms and glutathione-S-transferase M1 (GSTM1) and GSTT1 null mutation and the risk of polycystic ovary syndrome (PCOS) in Korean women. METHODS: This was a case-control study of 478 women with PCOS and 376 aged-matched healthy controls. Genotyping of the AhRR C/G polymorphism and GSTM1 and GSTT1 were performed using real-time PCR analysis and multiplex PCR, respectively. RESULTS: The genotype distribution of the AhRR C/G polymorphisms and GSTM1/GSTT1 null mutations did not differ between women with PCOS and controls. Using the wild-type combined AhRR CC and GSTT1 present genotype as a reference, the odds that a woman had PCOS were 1.54 (95% CIs 1.04-2.29) times higher if she had a combined AhRR CG or GG and GSTT1 null genotype. The odds that a woman had PCOS was 1.48 (95% CIs 1.08-2.04) times higher if she had a combined GSTM1/GSTT1 null genotype compared with the wild-type combined GSTM1/GSTT1 present genotype. However, there were no significant associations between the risk of PCOS and any combined AhRR and GSTM1. CONCLUSIONS: Our data suggest that a combined AhRR CG or GG and GSTT1 null genotype or a combined GSTT1/GSTM1 null genotype might be associated with an increased risk of PCOS.

Fas and FasL genetic polymorphisms in women with recurrent pregnancy loss: a case-control study.

Aberrant apoptosis at the trophoblast-maternal interface and abnormal expression of Fas and Fas ligand (FasL) have been reported in complicated pregnancies with recurrent pregnancy losses (RPL) and preeclampsia. We assessed the prevalence of Fas and FasL genetic polymorphisms in Korean women with RPL and in fertile controls. In total, 306 women with RPL and 298 fertile controls were enrolled. Genotype distributions of Fas and FasL in RPL patients versus fertile controls were examined under the Hardy-Weinberg equilibrium. Fas -670 A/G genotype (AA versus AG versus GG, p = 0.340) and allele frequencies (A versus G, p = 0.412) were not different between the RPL and control groups. There was no difference in each Fas -1377 G/A and FasL -844 C/T genotype, and their allele frequencies. In addition, the unions of two zygosities of each genotype and their combined genotypes did not differ between two groups. No difference in the prevalence of Fas and FasL single-nucleotide polymorphisms (SNPs) was observed between women with RPL and fertile controls among Korean women. To determine the possibility of genetic polymorphisms in Fas and its ligand as risk factors for RPL, further studies in various races and a large study population are needed.

Serum visfatin levels in non-obese women with polycystic ovary syndrome and matched controls.

OBJECTIVE: The purpose of the current study was to compare the circulating levels of visfatin between women with polycystic ovary syndrome (PCOS) and those without PCOS and to assess the correlations between visfatin levels and various parameters. METHODS: This case-control study recruited 74 PCOS patients and 74 age- and body mass index (BMI)-matched controls. Serum visfatin levels were evaluated using the enzyme-linked immunosorbent assay. Women with PCOS were divided into 2 subgroups based on the presence of clinical or biochemical hyperandrogenism. The possible differences in serum visfatin levels between the hyperandrogenic and non-hyperandrogenic groups were also assessed. RESULTS: Visfatin levels in PCOS patients were similar to those in the controls. However, hyperandrogenic patients had significantly higher mean serum visfatin levels than those in non-hyperandrogenic patients (3.87 ng/mL; 95% confidence intervals [CIs], 3.09-4.85 in hyperandrogenic group vs. 2.69 ng/mL; 95% CIs, 2.06-3.52 in non-hyperandrogenic group; P=0.038). In women with PCOS, visfatin levels positively correlated with BMI (r=0.23; P=0.047) and the log free androgen index (FAI) (r=0.27; P=0.021) and negatively correlated with high-density lipoprotein (HDL) cholesterol levels (r=-0.37; P=0.025). Except for HDL cholesterol levels, these correlations were also observed in controls. CONCLUSION: Visfatin levels in PCOS patients were similar to those in the controls. However, hyperandrogenic patients showed significantly higher serum visfatin levels than those of non-hyperandrogenic patients, and visfatin had a positive linear correlation with FAI in both PCOS patients and controls.

Prolactin receptor gene polymorphism and the risk of recurrent pregnancy loss: a case-control study.

Since the first study was published reporting the candidate association between the prolactin receptor gene intron C/T polymorphism (rs37389) and recurrent miscarriage, no replication study has been performed. In this study, we investigated the role of the prolactin receptor gene C/T polymorphism in 311 Korean women with recurrent pregnancy loss and 314 controls. Genotyping for prolactin receptor gene intron C/T polymorphism was performed using a TaqMan assay. The significance of difference in the genotype distribution was assessed using a chi-square test, and continuous variables were compared using a Student's t-test. The genotype distribution of the prolactin receptor gene C/T polymorphism in the recurrent pregnancy loss group did not differ from that in the control group (CC/CT/TT rates were 49.8%/41.5%/8.7% and 52.5%/37.6%/9.9% for the recurrent pregnancy loss patient and control groups, respectively, p = .587). When the analysis was restricted to patients with three or more consecutive spontaneous miscarriages or patients without prior live birth, there were also no differences in the genotype distribution between these subgroups and controls. In conclusion, the findings of the current study suggest that the prolactin receptor gene intron C/T polymorphism is not a major determinant of the development of recurrent pregnancy loss. Impact statement What is already known: Many studies have investigated whether there is a genetic component for the risk of recurrent pregnancy loss. Recently, one study investigated whether genetic polymorphisms involved in the regulation of the hypothalamic-pituitary-ovarian axis would be associated with recurrent miscarriage. Among 35 polymorphisms in 20 candidate genes, genotype distribution with regard to the prolactin receptor gene intron C/T polymorphism (rs37389) differed between the recurrent miscarriage and the control groups. Since this study reporting the candidate association between the prolactin receptor gene and recurrent miscarriage, no replication study has been performed. What the results of this study add: The genotype distribution of the prolactin receptor gene C/T polymorphism in the recurrent miscarriage group did not differ from that in the control group. What the implications are of these findings: Our study may be useful in that it is the first replication study since the initial report of the association of prolactin receptor gene polymorphism with recurrent miscarriage. Although no association was found, the potential role of prolactin in pregnancy loss needs to be further investigated because prolactin and its receptor have been postulated to play an important role in the maintenance of normal pregnancy.

Methylenetetrahydrofolate Reductase Polymorphisms and Risk of Recurrent Pregnancy Loss: a Case-Control Study.

The balance between coagulation and fibrinolysis is an essential part in early pregnancy. Mutations in methylenetetrahydrofolate reductase (MTHFR) gene lead to decreased activity of the enzyme and hyperhomocysteinemia, which then induces platelet aggregation by promoting endothelial oxidative damage, possibly resulting in adverse effect on maintenance of pregnancy. We investigated the role of MTHFR single nucleotide polymorphisms (SNPs), C677T and A1298C, in Korean patients with recurrent pregnancy loss (RPL). We conducted a prospective case-control study in the Korean population. Subjects included 302 women with 2 or more consecutive, unexplained, spontaneous miscarriages before 20 weeks of gestation and 315 control women without a history of recurrent miscarriages. The genotyping for C677T and A1298C polymorphisms was performed using the TaqMan assay. Continuous variables were compared using Student's t-test, and χ² test was used to evaluate differences in the genotype distributions between the RPL and the controls. The genotype distribution of both polymorphisms in the RPL group did not differ from those of the controls. For further analysis, if RPL patients were divided according to the numbers of pregnancy losses (≥ 2 and ≥ 3) neither group was significantly different compared with controls. MTHFR gene C677T and A1298C polymorphisms are not associated with idiopathic RPL in Korean women, suggesting that those may not be susceptible allelic variants or be deficient to cause RPL.

FSH receptor gene p. Thr307Ala and p. Asn680Ser polymorphisms are associated with the risk of polycystic ovary syndrome.

PURPOSE: The purpose of this study was to investigate whether the follicle-stimulating hormone receptor (FSHR) gene p. Thr307Ala (c.919A>G, rs6165) and p. Asn680Ser (c.2039A>G, rs6166) polymorphisms are associated with susceptibility to polycystic ovary syndrome (PCOS). METHODS: Genotyping was performed in 377 women with PCOS and 388 age-matched controls. Difference in the genotype distribution was assessed using a Fisher's exact or chi-square test, and continuous variables were compared using a Student's t test. To evaluate the association between the presence of PCOS status and SNP, logistic regression analyses were performed. RESULTS: Linkage disequilibrium between the two polymorphisms was approximately complete (r 2 = 99%). The genotype distributions of the PCOS group significantly differed from those of the control group (Thr/Thr, Thr/Ala, and Ala/Ala frequencies were 38.5, 46.7, and 14.9% for the PCOS group and 46.6, 45.4, and 8.0% for the controls, respectively, P = .005; Asn/Asn, Asn/Ser, and Ser/Ser frequencies were 39.5, 47.2, and 13.3% for the PCOS group and 46.4, 45.4, and 8.2% for the controls, respectively, P = .035). Using the wild-type genotypes as the references, the odds ratios that a woman has PCOS were 2.23 (95% confidence intervals 1.38-3.68) for the Ala/Ala genotype, 1.87 (95% confidence intervals 1.14-3.06) for the Ser/Ser genotype, and 1.96 (95% confidence intervals 1.19-3.24) for the homozygous variant combination (Ser/Ser-Ala/Ala). However, there were no significant differences in serum hormonal, ovarian, and metabolic markers according to each genotype. CONCLUSIONS: Findings of this study suggest a significant association between FSHR gene p. Thr307Ala or p. Asn680Ser coding sequence change and PCOS. The variant homozygote genotype results in a higher risk of PCOS.

Estrogen receptor beta gene polymorphisms and risk of recurrent pregnancy loss: a case-control study.

Estrogen might play a key role in the maintenance of pregnancy. We investigated the role of the ER-ß gene +1730 G/A, +1082 G/A, and CA repeat polymorphisms in Korean patients with recurrent pregnancy loss (RPL). Genotyping was performed using the TaqMan assay in 305 patients with at least two unexplained consecutive spontaneous miscarriages before 20 weeks of gestation and 299 controls. The genotype distributions of the ER-ß gene +1082 G/A and +1730 G/A polymorphisms in the RPL group did not differ from those in the control group. When the analysis was restricted to patients with three or more consecutive spontaneous miscarriages, there were also no differences in the genotype distribution between this subgroup and controls. The number of CA repeats was distributed from 13 to 28 with two large peaks at 18 and 23 in patients with RPL and controls. Using the two major peaks as cut-offs, the allele distributions were compared between patients and controls. However, the distribution of ER-ß gene CA repeats did not differ between women with recurrent miscarriage and controls. Findings of the current study suggest that the ER-ß gene polymorphisms are not major determinants of the development of RPL in Korean women.

No association of p53 codon 72 polymorphism with idiopathic recurrent pregnancy loss in Korean population.

OBJECTIVE: The balance of apoptosis and proliferation is an important part in the embryonic development during pregnancy. It has been reported that the p53 gene plays a significant role in angiogenesis and placental development, namely in reproduction and is suggested as a potential mediator of pregnancy. This study was performed to investigate whether the genetic polymorphism of the p53 gene is associated with idiopathic recurrent pregnancy loss (RPL). STUDY DESIGN: We conducted a case-control study in the Korean population. Study subjects consisted of 294 patients with idiopathic RPL and 300 postmenopausal controls. The genotyping for the p53 codon 72 polymorphism was performed using a Taqman assay. Continuous variables were compared using Student's t test and the χ(2) test was used to evaluate differences in the genotype distributions between the RPL and the controls. RESULTS: There were no significant differences in the genotype distributions or allele frequencies of the p53 codon 72 polymorphism between the RPL and control group. There was also no significant association between the p53 codon 72 polymorphism and RPL risk in both recessive (Pro/Pro vs. Arg-carriers, p=0.314) and dominant model (Pro-carriers vs. Arg/Arg, p=0.383: data not shown). CONCLUSION: The codon 72 polymorphism in the p53 gene did not show any correlation with idiopathic RPL in Korean women, implying that it may not be susceptible allelic variants or be insufficient to cause RPL.

The PAI-1 4G/5G and ACE I/D polymorphisms and risk of recurrent pregnancy loss: a case-control study.

PROBLEM: 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. METHOD OF STUDY: Genotyping was performed using the TaqMan assay in 227 RPL patients and 304 controls. RESULTS: The genotype distributions of both polymorphisms in the RPL group did not differ from those of controls. Because the frequency of being homozygous for ACE D/D and the PAI-I 4G/4G combination has been reported to be significantly higher in RPL patients, this was also analyzed. However, no significant difference was noted; 3.1% of RPL patients had both ACE D/D and PAI-I 4G/4G, as did 4.9% of controls (P = 0.791). CONCLUSION: The current study suggests that both polymorphisms, either alone or in combination, are not major determinants of the development of RPL in Korean women.

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.

Gene dose effect between a fat mass and obesity-associated polymorphism and body mass index was observed in Korean women with polycystic ovary syndrome but not in control women.

OBJECTIVE: To examine the association between fat mass and obesity-associated (FTO) polymorphisms and polycystic ovary syndrome (PCOS) in Korean women. DESIGN: Case-control study. SETTING: University department of obstetrics and gynecology. PATIENT(S): Women with (n = 552) or without (n = 559) PCOS. INTERVENTION(S): Genotyping was performed. MAIN OUTCOME MEASURE(S): FTO rs9939609 genotype distribution and correlation between variants in this gene and PCOS phenotypes. RESULT(S): The mean body mass index (BMI) of the patients was significantly higher than that of the control subjects (22.0 ± 4.1 kg/m(2) vs. 20.1 ± 2.5 kg/m(2)), but most (81.3%) of the patients were not obese. FTO rs9939609 was not significantly associated with PCOS itself. However, a positive correlation was observed between the number of variant alleles and BMI in women with PCOS: Each additional copy of the variant allele increased BMI by a mean (95% confidence interval) of 4.8% (1.4%-8.3%) or 1.11 kg/m(2) (1.03-1.20 kg/m(2)) after adjusting for age. This correlation was not observed in the control subjects. CONCLUSION(S): FTO rs9939609 was not a major determinant of PCOS. However, in the women with PCOS who were primarily nonobese, a gene dose effect was observed for BMI. The FTO gene may play an influential role in predisposition to PCOS via an association with obesity.

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.

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

OBJECTIVE: 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. DESIGN: Case-control study. PATIENTS: Women with or without PCOS. MEASUREMENTS: DNA samples from 377 patients with PCOS and 386 age-matched controls were genotyped. RESULTS: None of the 12 SNPs in the six genes (KCNJ11, TCF7L2, SLC30A8, HHEX, FTO and CDKAL1) uncovered in the genome-wide association studies were associated with PCOS. For further analysis, the patients with PCOS were divided into two or three subgroups according to genotype, and the associations between the genotypes and insulin resistance or insulin secretory capacity were assessed. No SNPs were significantly associated with HOMA-IR, HOMA (ßcell) (%), or 2-h 75-g oral glucose tolerance test insulin levels in the patients with PCOS; there were no significant associations with other serum hormonal and metabolic markers, such as androgen or glucose levels. CONCLUSIONS: Our results suggest that the six type 2 diabetes-associated genes identified in genome-wide association studies are not associated with PCOS.

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.

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

PROBLEM: To investigate whether the glutathione-S-transferase P1 (GSTP1) exon 5 polymorphism is associated with susceptibility to advanced stage endometriosis in Korean women. METHOD OF STUDY: Case-control study in a collective of 260 patients and 164 controls. Genotyping of the GSTP1 exon 5 polymorphism was performed by using real-time TaqMan PCR assay. RESULTS: The genotype distribution of the GSTP1 exon 5 polymorphism in the endometriosis group was not significantly different from that of the control group (AA/AG/GG rates were 64.2%/32.7%/3.1% and 65.2%/31.7%/3.0% for the endometriosis and control groups, respectively, P = 0.977). Further subgroup analysis according to either stage or bilaterality of ovarian endometrioma also found no significant difference in the genotype distribution between any of the endometriosis subgroups and the control group. CONCLUSION: These findings suggest that the GSTP1 exon 5 polymorphism is not a major determinant of the development of advanced stage endometriosis in the Korean population.

Estrogen receptor {alpha} 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.

Interleukin-2 receptor beta 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.

Phosphatidylinositol 3-kinase p85alpha 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.

Association of tumor necrosis factor-{alpha} 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.