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Association of adiponectin gene polymorphism with polycystic ovarian syndrome
A-353 COMPARISON OF PREGNANCY OUTCOME IN PCOS PATIENTS AFTER INFERTILITY TREATMENT WITH LETROZOLE OR CLOMIPHENE CITRATE. T. Segawa, K. Shinohara, O. Miyauchi, S. Kawachiya, Y. Takehara, O. Kato. Kato Ladies Clinic, Tokyo, Japan. OBJECTIVE: The first line treatment for ovulatory disorders like polycystic ovary syndrome (PCOS) for more than 40 years has been clomiphene citrate (CC). In women with PCOS, because of the high sensitivity of the ovaries with CC or hMG, the treatment is difficult to control and induces several ovulatory follicles. Recently, clinical evidence showed that aromatase inhibitor letrozole could be used as an alternative to CC in ovulation induction. In this study, we aimed to investigate the pregnancy outcome of infertile PCOS patients who conceived with letrozole compared to CC. DESIGN: Prospective non-randomized study. MATERIALS AND METHODS: Between October 2003 to July 2007, we identified 104 clinical pregnancies from PCOS women who conceived following letrozole or CC treatment at our clinic. Informed consent for patients was obtained before this study. All patients had to have infertility period more than one year, and had no tubal and no male factor. The patients in the letrozole group (n¼73) were given 2.5 mg letrozole for 5 days from day 3 of their menstrual cycle. The patients in the CC group (n¼31) were given 100 mg CC for 5 days starting from day 3. In both groups, hMG were given at a dose of 75-150 IU every other day starting on day 8 or 10. When dominant follicles reached to a diameter of 18-20 mm, we administered 600mg GnRH analogue to trigger endogenous LH surge. All patients were advised to have timed intercourse at the time of ovulation. Clinical pregnancy was confirmed by observing gestational sac at 3 weeks after timed intercourse. RESULTS: There was no difference in patients’ age (31.72.7 vs. 32.13.6 years, NS), duration of infertility (4.02.7 vs. 4.02.6 years, NS), body mass index(20.63.2 vs. 20.74.2, NS), and serum gonadotropin level on cycle day 3 (LH: 10.95.9 vs. 13.14.1 mIU/ml, FSH: 8.42.8 vs. 7.92.7 mIU/ml, NS) between letrozole and CC groups. Clinical abortion rate was almost similar among two groups (16.1 vs. 15.1%, NS). The birth weights of the newborns among the two groups were also similar(2875582g vs. 2892608g, NS). The incidence of male babies was lower in letrozole group (35.7%) than CC group (52.2%), but not significant. Major congenital malformations of babies were not detected in both groups. CONCLUSIONS: In this study, there was no difference in pregnancy outcome from PCOS patients who conceived after letrozole or CC treatments. Although letrozole use for ovulation induction may not be toxic based on our data, we have to need further study and confirm drug safety more. Supported by: None.
A-354 CATECHOL-O-METHYLTRANSFERASE GENE POLYMORPHISM IN WOMEN WITH POLYCYSTIC OVARY SYNDROME. Y. Ku, S. J. Chae, J. J. Kim, G. R. Hwang, S.-Y. Ku, Y. M. Choi. Department of Obstetrics and Gynecology, College of Medicine, Seoul National University, Seoul, Republic of Korea; Maria Fertility Hospital, Seoul, Republic of Korea. Seoul National University Boramae Hospital, Seoul, Republic of Korea. OBJECTIVE: Polycystic ovary syndrome (PCOS) is the most common cause of anovulation in women of reproductive age. One of the characteristic features of PCOS is the arrest of follicular maturation. Catechol-O-methyltransferase (COMT) is the principal enzyme in conjugation and inactivation of the catechol estrogens. Overexpression of COMT, which is prevalent in PCOS, increases the level of 2-methoxyestradiol in granulosa cells and leads to ovulatory dysfunction. The COMT gene G/A single nucleotide polymorphism at codon 158 results in substitution of methionine to valine, which is associated with 3-4 folds decreased enzyme activity. We attempted to evaluate the association between COMT gene polymorphism and PCOS. DESIGN: Case control study. MATERIALS AND METHODS: The COMT genotypes were determined in 156 PCOS patients and 116 controls by PCR-RFLP method. To evaluate the effect of the COMT genotype on the phenotype, PCOS patients were classified into four groups as follows: 1) irregular menstruation (IM), hyperandrogenism (HA) and polycystic ovary (PCO), 2) IM and PCO, 3) IM and HA and 4) HA and PCO. Chi square test was conducted as appropriate and a p value of < .05 was considered as statistically significant. RESULTS: The COMT genotype distributions in both PCOS patients and the controls were in the Hardy-Weinberg equilibrium. Genotype distribution of the COMT gene was not different between PCOS patients and the controls (G/G of 50.6% vs. 52.2%, G/A of 41.0% vs. 38.2%, and A/A of 8.3% vs.
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Abstracts
11.2%, respectively). There was also no difference in the G and A allele frequencies between the two groups (71.2% vs. 71.6%, and 28.8% vs. 28.4%, respectively). The COMT genotype distribution of the each subgroup of PCOS patients was not statistically different from that of the controls (p values were .89 for group 1), .14 for group 2), .21 for group 3) and .81 for group 4)). TABLE 1. Distribution of COMT gene polymorphism SNP rs898611 genotype
Allele frequency
Group AA
AG
GG
p
A
G
p
PCOS (n¼156)
13 (8.3%)
64 (41.0%)
79 (50.6%)
.474 *
90 (28.8%)
222 (71.2%)
.919 *
Control (n¼116)
13 (11.2%)
40 (38.2%)
63 (52.2%)
66 (28.4%)
166 (71.6%)
* c2-test in comparison with the control group. CONCLUSIONS: These results suggest that codon 158 G/A polymorphism of the COMT gene is not associated with the risk of PCOS in the Korean population. Phenotype of PCOS was also not affected by the COMT genotype. Supported by: A grant from the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (01-PJ10-PG6-01GN13-0002). A-355 ASSOCIATION OF ADIPONECTIN GENE POLYMORPHISM WITH POLYCYSTIC OVARIAN SYNDROME. X. Xia, Y. Cao. Reproductive Medicine Center, First Affiliated Hospital Anhui Medical University, Hefei, China. OBJECTIVE: To investigate the frequency of rs2241766 and rs1501299 of adiponectin gene and to elucidate its role in the pathogenesis of PCOS, and hope to estabolish foundation to support the diagnosis and treatment of PCOS. DESIGN: Prospective study. MATERIALS AND METHODS: Whole genome DNA of 280 patients with PCOS and 256 healthy people were gathered and genotyped by Polymerase Chain Reaction Restriction Fragment Length Polmorphism (PCRRFLP). RESULTS: (1) The genotype frequencies of rs2241766 (TT/TG/GG) in the PCOS group were 60%, 35.7%, 4.3% and in control group were 39.9%, 50.4%, 9.7%, respectively. The genotype frequencies of rs1501299 (TT/TG/GG) in the PCOS group were 7.1%, 29.3%, 63.6% and in control group were 17.2%, 40.7%, 46.1%, respectively. The genotype frequencies of T and C in PCOS patients was significantly higher than that of the control group(P<0.01). (2)The C and T allele frequencies of rs 2241766 in adiponectin gene in the PCOS group were 77.86%, 22.14% and in control group were 65.12%, 34.88%, respectively. The C and T allele frequencies of rs1501299 in adiponectin gene in PCOS group were 23.91%, 76.09% and in control group were 33.53%, 66.47%, respectively. The allele frequencies of rs2241766 and rs1501299 of PCOS were significantly higher than healthy group (P<0.01). CONCLUSIONS: Adiponectin gene is related with PCOS, it may be one of susceptive gene of PCOS. Supported by: None. A-356 POLYMORPHISMS IN POST-INSULIN RECEPTOR SIGNALING PATHWAY IN SAUDI WOMEN WITH POLYCYSTIC OVARY SYNDROME. A. A. Rouzi, M. S. Ardawi. King Abdulaziz University, Jeddah, Saudi Arabia. OBJECTIVE: To determine whether post-insulin receptor signaling polymorphism (including PIK3R1, SLC2A4, SLC2A4RG and MEF2A genes) are associated with susceptibility to polycystic ovary syndrome (PCOS) or to insulin resistance (IR) of PCOS. DESIGN: A prospective Case Control Study. MATERIALS AND METHODS: Two hundred Saudi women living in the Jeddah area were classified as follows: 100 with PCOS and 100 age-matched women without PCOS. Blood samples were collected from all women with or without PCOS between 8:00-11:00, after an overnight fast. Frequency of PIK3RI, SLC2A4, SLC2A4RG and MEF2A polymorphisms in women with and without PCOS was determined.
Vol. 90, Suppl 1, September 2008
A-354 CATECHOL-O-METHYLTRANSFERASE GENE POLYMORPHISM IN WOMEN WITH POLYCYSTIC OVARY SYNDROME. Y. Ku, S. J. Chae, J. J. Kim, G. R. Hwang, S.-Y. Ku, Y. M. Choi. Department of Obstetrics and Gynecology, College of Medicine, Seoul National University, Seoul, Republic of Korea; Maria Fertility Hospital, Seoul, Republic of Korea. Seoul National University Boramae Hospital, Seoul, Republic of Korea. OBJECTIVE: Polycystic ovary syndrome (PCOS) is the most common cause of anovulation in women of reproductive age. One of the characteristic features of PCOS is the arrest of follicular maturation. Catechol-O-methyltransferase (COMT) is the principal enzyme in conjugation and inactivation of the catechol estrogens. Overexpression of COMT, which is prevalent in PCOS, increases the level of 2-methoxyestradiol in granulosa cells and leads to ovulatory dysfunction. The COMT gene G/A single nucleotide polymorphism at codon 158 results in substitution of methionine to valine, which is associated with 3-4 folds decreased enzyme activity. We attempted to evaluate the association between COMT gene polymorphism and PCOS. DESIGN: Case control study. MATERIALS AND METHODS: The COMT genotypes were determined in 156 PCOS patients and 116 controls by PCR-RFLP method. To evaluate the effect of the COMT genotype on the phenotype, PCOS patients were classified into four groups as follows: 1) irregular menstruation (IM), hyperandrogenism (HA) and polycystic ovary (PCO), 2) IM and PCO, 3) IM and HA and 4) HA and PCO. Chi square test was conducted as appropriate and a p value of < .05 was considered as statistically significant. RESULTS: The COMT genotype distributions in both PCOS patients and the controls were in the Hardy-Weinberg equilibrium. Genotype distribution of the COMT gene was not different between PCOS patients and the controls (G/G of 50.6% vs. 52.2%, G/A of 41.0% vs. 38.2%, and A/A of 8.3% vs.
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Abstracts
11.2%, respectively). There was also no difference in the G and A allele frequencies between the two groups (71.2% vs. 71.6%, and 28.8% vs. 28.4%, respectively). The COMT genotype distribution of the each subgroup of PCOS patients was not statistically different from that of the controls (p values were .89 for group 1), .14 for group 2), .21 for group 3) and .81 for group 4)). TABLE 1. Distribution of COMT gene polymorphism SNP rs898611 genotype
Allele frequency
Group AA
AG
GG
p
A
G
p
PCOS (n¼156)
13 (8.3%)
64 (41.0%)
79 (50.6%)
.474 *
90 (28.8%)
222 (71.2%)
.919 *
Control (n¼116)
13 (11.2%)
40 (38.2%)
63 (52.2%)
66 (28.4%)
166 (71.6%)
* c2-test in comparison with the control group. CONCLUSIONS: These results suggest that codon 158 G/A polymorphism of the COMT gene is not associated with the risk of PCOS in the Korean population. Phenotype of PCOS was also not affected by the COMT genotype. Supported by: A grant from the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (01-PJ10-PG6-01GN13-0002). A-355 ASSOCIATION OF ADIPONECTIN GENE POLYMORPHISM WITH POLYCYSTIC OVARIAN SYNDROME. X. Xia, Y. Cao. Reproductive Medicine Center, First Affiliated Hospital Anhui Medical University, Hefei, China. OBJECTIVE: To investigate the frequency of rs2241766 and rs1501299 of adiponectin gene and to elucidate its role in the pathogenesis of PCOS, and hope to estabolish foundation to support the diagnosis and treatment of PCOS. DESIGN: Prospective study. MATERIALS AND METHODS: Whole genome DNA of 280 patients with PCOS and 256 healthy people were gathered and genotyped by Polymerase Chain Reaction Restriction Fragment Length Polmorphism (PCRRFLP). RESULTS: (1) The genotype frequencies of rs2241766 (TT/TG/GG) in the PCOS group were 60%, 35.7%, 4.3% and in control group were 39.9%, 50.4%, 9.7%, respectively. The genotype frequencies of rs1501299 (TT/TG/GG) in the PCOS group were 7.1%, 29.3%, 63.6% and in control group were 17.2%, 40.7%, 46.1%, respectively. The genotype frequencies of T and C in PCOS patients was significantly higher than that of the control group(P<0.01). (2)The C and T allele frequencies of rs 2241766 in adiponectin gene in the PCOS group were 77.86%, 22.14% and in control group were 65.12%, 34.88%, respectively. The C and T allele frequencies of rs1501299 in adiponectin gene in PCOS group were 23.91%, 76.09% and in control group were 33.53%, 66.47%, respectively. The allele frequencies of rs2241766 and rs1501299 of PCOS were significantly higher than healthy group (P<0.01). CONCLUSIONS: Adiponectin gene is related with PCOS, it may be one of susceptive gene of PCOS. Supported by: None. A-356 POLYMORPHISMS IN POST-INSULIN RECEPTOR SIGNALING PATHWAY IN SAUDI WOMEN WITH POLYCYSTIC OVARY SYNDROME. A. A. Rouzi, M. S. Ardawi. King Abdulaziz University, Jeddah, Saudi Arabia. OBJECTIVE: To determine whether post-insulin receptor signaling polymorphism (including PIK3R1, SLC2A4, SLC2A4RG and MEF2A genes) are associated with susceptibility to polycystic ovary syndrome (PCOS) or to insulin resistance (IR) of PCOS. DESIGN: A prospective Case Control Study. MATERIALS AND METHODS: Two hundred Saudi women living in the Jeddah area were classified as follows: 100 with PCOS and 100 age-matched women without PCOS. Blood samples were collected from all women with or without PCOS between 8:00-11:00, after an overnight fast. Frequency of PIK3RI, SLC2A4, SLC2A4RG and MEF2A polymorphisms in women with and without PCOS was determined.
Vol. 90, Suppl 1, September 2008