Androgen receptor cytosine, adenine, and guanine trinucleotide repeat polymorphism in Korean patients with endometriosis: A case-control study.

STUDY OBJECTIVE: To investigate the association between the androgen receptor (AR) cytosine, adenine, and guanine (CAG) repeat polymorphisms and endometriosis. STUDY DESIGN: A prospective case-control, genetic association study was performed on women with surgically proven endometriosis (n=421) and controls free of endometriosis (n=349). AR CAG repeat lengths were determined from peripheral blood samples. The difference in the frequency of each alleles were compared in patients with endometriosis and controls using Chi-square test. MAIN RESULTS: No significant difference in biallelic length mean between patients and controls was observed. Alleles containing 24 CAG repeats were significantly more frequent in stage I-II (mild) endometriosis than in the control samples (19.8% and 13.3%, respectively; OR 1.60, 95% CI 1.04-2.47). Additionally, a higher frequency of both alleles with 24 or more CAG repeats was observed in individuals with mild endometriosis, in comparison with the controls (25.6% and 15.2%, respectively; OR 1.92, 95% CI 1.09-3.38). CONCLUSIONS: AR gene CAG repeat polymorphisms are associated with the increased risk of mild endometriosis.

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.

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.

Prevalence of metabolic syndrome is higher among non-obese PCOS women with hyperandrogenism and menstrual irregularity in Korea.

BACKGROUND: Hyperandrogenism (HA) has been linked with several components of metabolic syndrome (MetS). Few studies in Asian women have evaluated the important risk factors for and prevalence of MetS according to PCOS subtype. In this study, we investigated differences in metabolic parameters and the prevalence of MetS in two major phenotypic subgroups of PCOS in Korea. Furthermore, we investigated the relationship between HA-associated parameters and MetS. MATERIALS AND METHODS: This cross-sectional observational study was conducted from May 2010 to December 2011 in Korea. A total of 837 females with PCOS, aged 15-40, were recruited from Departments of Obstetrics and Gynecology at 13 hospitals. Of those, 700 subjects with either polycystic ovaries (PCO)+HA+oligomenorrhea/amenorrhea (O) or PCO+O were eligible for this study. MetS was diagnosed according to the modified National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III guidelines and the International Diabetes Federation (IDF) criteria. RESULTS: MetS was more prevalent in the PCO+HA+O group (19.7%) than in the PCO+O (11.9%) group. There were statistically significant trends for an increased risk of MetS in the PCO+HA+O group compared to the PCO+O group. After adjustment for age, the odds ratio of MetS was 2.192 in non-obese subjects with PCO+HA+O compared to those with PCO+O, whereas the risk of MetS was not different in obese patients. Multivariate logistic regression analysis showed that high free androgen index and low sex hormone-binding globulin were significantly associated with MetS in non-obese women with PCOS, with odds ratios of 4.234 (95% CI, 1.893-9.474) and 4.612 (95% CI, 1.978-10.750), respectively. However, no associations were detected between MetS and SHBG and FAI in obese PCOS subjects. CONCLUSIONS: Our results indicate that HA and its associated parameters (FAI and SHBG) are significantly associated with MetS in non-obese PCOS subjects, whereas this association was not observed in obese subjects.

Uterine infarction in a patient with uterine adenomyosis following biochemical pregnancy.

Adenomyosis is a common gynecological disorder characterized by the presence of endometrial glands and stroma deep within the myometrium associated with myometrial hypertrophy and hyperplasia. Focal uterine infarction after IVF-ET in a patient with adenomyosis following biochemical pregnancy has not been previously reported, although it occurs after uterine artery embolization in order to control symptoms caused by fibroids or adenomyosis. We report a case of a nulliparous woman who had uterine adenomyosis presenting with fever, pelvic pain and biochemical abortion after undergoing an IVF-ET procedure and the detection of a slightly elevated serum hCG. Focal uterine infarction was suspected after a pelvic magnetic resonance imaging demonstrated preserved myometrium between the endometrial cavity and inner margin of the necrotic myometrium. This case demonstrates that focal uterine infarction should be considered in the differential diagnosis of acute abdominal pain, vaginal bleeding and infectious signs in women experiencing biochemical abortion after an IVF-ET procedure.