한국인 임신성 고혈압 임부에서 Angiotensin 2 제 1 형 수용체 유전자의 다형성 A1166C에 대한 분석

최훈 ( Hoon Choi ),김복린 ( Bok Rin Kim ),이홍균 ( Hong Kyoon Lee ),조용균 ( Yong Kyoon Cho ) 대한주산의학회 2002 Perinatology Vol.13 No.3

연구목적:근래에 Renin-angiotensin(RA) 유전자 시스템과 자간전증과의 연관성이 검토되어 왔다. Angiotensinogen 유전자 단일염기 다형성인 M235T, T174M을 비롯하여 angiotensin Ⅰ 전환효소의 I/D 다형성과의 관련성이 최근 집중적으로 연구되었는데 인종과 지역, 민족에 따라 그 상관관계의 편차가 심한 것으로 판명되고 있다. 한국인 임신성 고혈압 임부를 대상으로 한 연구에서도 Angiotensinogen 유전자 다형성인 M235T, T174M은 임신성 고혈압과 관련성이 없었고, angiotensin-converting enzyme I/D 다형성의 경우 증세가 심한 경우에만 관련성 여부가 추론 되고 있으나 역시 한국인 임부에서는 관련성이 미약했다. 반면 Angiotensin Ⅱ 제 1 형 수용체 유전자 다형성 A1166C의 경우 RA 유전자 시스템 중 다른 유전자 다형성과는 관련성이 없더라도 이 수용체 다형성은 직접적인 관련성이 있다는 결과가 최근 서양인과 중국인에서 보고 되고 있다. 따라서 본 연구에서는 한국인 임신성 고혈압 임부 121예와 정상 분만한 대조군 98예를 통하여 그 관련성을 규명 하고자 하였다. 방법:121예의 임신성 고혈압 임부와 98예의 정상 분만한 임부를 대조군으로 하여 임파구안의 유전체를 순수 정제한 다음 angiotensin Ⅱ 제 1 형 수용체 유전자 다형성 A1166C의 유전형을 PCR-RFLP (Restriction fragment length polymorphism) 방법을 이용하여 규명하였다. 인간 DNA를 100ng 정도 이용하여 두 종류의 프라이머(sense 5`-CGA CTA CTG CTT AGC ATA-3`, antisense 5`-GCA CCA TGT TTT GAG GTT-3`)를 0.2μM 첨가하고 전체 반응 부피 20μL에서 50 mM KCl, 10mM Tris-HCl(pH 8.4), 2.5mM MgCl2, 0.01% gelatin, 250μM deoxynucleotide triphosphate 그리고 2unit의 Taq DNA polymerase를 첨가 하였다. 95℃에서 5분 동안 초기 변성 시킨 다음 94℃ 1분, 58℃ 1분, 72℃에서 2분을 총 30회 반복하여 증폭조건을 확립하였다. 546bp의 PCR 산물을 2% 아가로즈 전기영동을 통하여 분석하고 DdeI 제한효소를 이용하여 RFLP분석을 시행하였다. 대립인자 C는 435bp와 111bp의 두 종류의 단편으로 나타났으며 대립인자 A의 경우 DdeI 제한효소에 잘리지 않아 546bp의 단편으로 나타났다. 결과:121예의 임신성 고혈압 임부와 98예의 정상 분만한 임부를 포함한 총 219예의 임부에서 A1166/C1166형과 A1166/A1166형의 빈도는 임신성 고혈압 임부에서는 9.9%(12명)와 90.1%(109명), 그리고 대조 임부군에서는 17.3%(17명)와 82.7%(81명)로 통계적으로 유의성은 없었으며(p=0.106), C1166/C1166 유형은 나타나지 않았다. 결론:한국인 임신성 고혈압에 대한 분자병인 연구에 있어서 Angiotensin Ⅱ 제 1 형 수용체 유전자 다형성 A1166C는 임신성 고혈압의 발생과는 관련이 없는 것으로 사료되며, 대립인자 C형이 한국인 임신성 고혈압 임부 군에서는 기존에 보고 된 위험요인이 아닌 보호 역할을 하는 경향으로 나타나 대규모 연구가 필요하다고 사료된다. Background/Aim:Recent studies have suggested an association between genetic background of renin-angiotensin(RA) system and the pathogenesis of pregnancy induced hypertension(PIH). Even though various single nucleotide polymorphism(SNP) such as M235T, T174M polymorphism in angiotensinogen gene(AGT) and I/D polymorphism in angiotensin I-converting enzyme gene(ACE) have been studied extensively among essential hypertension and PIH in various population, its association was still inconclusive. Previous studies within Korean PIH patients also revealed that M235T or T174M single nucleotide polymorphism in AGT gene or I/D polymorphism in ACE gene were not linked tightly with PIH. However, recent studies on angiotensin II type I receptor(AT1) polymorphism A1166C with PIH in Polish or in Chinese suggested its possible correlations to a pathogenesis of PIH. Thus the aim of the present study was to determine the frequency of genotypes of A1166C mutation in women with PIH and to establish the role of this polymorphism on the susceptibility to the PIH development. Patients and Methods:We have analysed 121 women with PIH and 98 healthy normotensive gravid women as a control. Genomic DNA was used for PCR. To genotype the A1166C polymorphism in angiotensin II receptor(AT1) gene, primers(sense 5`-CGA CTA CTG CTT AGC ATA-3`, antisense 5`-GCA CCA TGT TTT GAG GTT-3`) were employed to make 546bp PCR product. There was an initial denaturation at 94℃ 5 minutes, followed by 30 cycles of one minute at 94℃, one minute at 58℃, and two minutes at 7℃. A 546bp PCR product was further digested with DdeI for 2 hour at 37℃ and analysed through 2% agarose gel electrophoresis to determine genotype. Allele C1166 yielded 435bp, 111bp fragment and allele A1166 yielded intact 546 bp fragment. Results:We found that frequency of genotype A1166/C1166 and A1166/A1166 in PIH were 9.9%(12) and 90.1%(109), while in controls were 17.3%(17) and 82.7%(81). There was no statistical significance between development of PIH and A1166C polymorphism in type I receptor for Angiotensin II. Homozygous mutated genotype(C1166/C1166) was not detected in this study. Conclusion:Our results found no possible correlation of A1166C polymorphism in angiotensin II receptor(AT1) with PIH in Korean and found that allele C might behave as a protective factor rather than as a risk factor in the pathogenesis of PIH. We suggest a large-scale study to evaluate relevance to this polymorphism for PIH.

자간전증 임신부의 Tumor Necrosis Factor-α(TNF-α)의 혈청농도

조용균 ( Yong Kyoon Cho ),박교훈 ( Kyo Hoon Park ),최훈 ( Hoon Choi ),김복린 ( Bok Rin Kim ),이홍균 ( Hong Kyoon Lee ) 대한주산의학회 2000 大韓周産醫學會雜誌 Vol.11 No.1

자간전증이 prostaglandin E2 및 oxytocin을 사용한 분만유도에 미치는 영향

박교훈(Kyo Hoon Park),조용균(Yong Kyoon Cho),최훈(Hoon Choi),김복린(Bok Rin Kim),한성식(Sung Shik Han),이철민(Chul Min Lee),이홍균(Hong Kyoon Lee) 대한산부인과학회 2001 Obstetrics & Gynecology Science Vol.44 No.3

Objective : The purposes of this study were 1) to determine whether preeclampsia itself affects failure of labor induction with prostaglandin E2 and oxytocin and 2) to investigate risk factors for failed induction in women with preeclampsia. Method : Fifty preeclamptic women and 175 nonpreeclamptic women requiring labor induction were studied prospectively. Intravaginal prostaglandin (PG) E2 tablet (Dinoprostone, The Upjohn company, 3 mg) followed by a second dose if the cervix assessed 6 hours later was 5 or less of Bishop score, and oxytocin were used for labor induction. Women with rupture of membrane, spontaneous contraction resulting in cervical change or an initial cervical examination showing more than 2 cm dilatation and 50% effacement were excluded. Statistics were analyzed with 2 test, Student t test, and multiple logistic regression. Results : 1) The women with preeclampsia had a significantly higher rate of failed induction than did those without preeclampsia [24% (2/50) versus 9% (16/175); p <0.05]. However, the women with preeclampsia had a higher rate of the use of magnesium sulfate, and were more likely to decrease gestational age at induction and increase maternal weight than those without preeclampsia (p <0.0001, respectively). There were no significant differences in prevalence of nulliparity and low initial Bishop score (≤3) between the women with and without preeclampsia. 2) Multiple logistic regression showed that preeclampsia itself was not associated with failed induction after correction of known confounding variables (odds ratio 0.22, 95% confidence interval 0.03-2). 3) In women with preeclampsia, the use of magnesium sulfate only was associated with increased risk of failed induction analyzed by multiple logistic regression(odds ratio 38.5, 95% confidence interval 1.6-897). Maternal weight with 70 kg or more was associated with increased risk of failed induction, but it is not statistically significant (p=0.055). Conclusion : 1) The risk of failed induction is increased in women with preeclampsia, but not by preeclampsia itself but by the use of magnesium sulfate, prematurity, and increased maternal weight secondary to preeclampsia. 2) The use of magnesium sulfate is independent risk factor for failed induction in women with preeclampsia.

성숙 기형종에서 유래한 진행성 난소 편평상피세포암

강웅선 ( Woong Sun Kang ),이철민 ( Chul Min Lee ),임성직 ( Sung Jig Lim ),조용균 ( Yong Kyoon Cho ),최훈 ( Hoon Choi ),김복린 ( Bok Rin Kim ),이홍균 ( Hong Kyoon Lee ) 대한산부인과학회 2003 Obstetrics & Gynecology Science Vol.46 No.2

Mature cystic teratoma comprises approximately 10-20% of all ovarian neoplasms and malignant transformation from mature cystic teratoma is reported to be less than 2%. Squamous cell carcinoma is the most frequent malignancy (80%) arising in mature cystic

자간전증 임신부의 Vascular Endothelial Growth Factor ( VEGF ) 의 혈청농도

조용균(Yong Gyun Jo),민현주(Hyun Joo Min),박교훈(Gyo Hoon Park),최훈(Hoon Choi),김복린(Bok Rin Kim),이홍균(Hong Gyun Lee) 대한산부인과학회 2000 Obstetrics & Gynecology Science Vol.43 No.11

Objective : To assess whether there is correlation between serum concentrations of vascular endothelial growth factor(VEGF) and development of preeclampsia. Methods : The authors measured serum concentrations of VEGF in 18 preeclamptic women admitted to Sanggye Paik Hospital, Inje University from February 1999 to September 1999 and in 18 normotensive pregnant women matched in maternal age, maternal body weight, parity and gestational age. VEGF was measured with a sensitive and specific enzyme immunoassays. Results : VEGF was detected in all pregnant women. The results of this study showed that the serum concentrations of VEGF are significantly higher in the preeclamptic women than in the normotensive pregnant women. The values of median and range of VEGF are 7.74 ng/ml and 0.5-35.94 ng/ml in the preeclamptic women, and 0.5 ng/ml and 0.5-2.16 ng/ml in the normotensive pregnant women, respectively. There is significant difference in serum concentrations of VEGF between two groups(p<0.001, Mann-Whitney U test). Positive correlations were noted between VEGF concentraions and the systolic and diastolic blood pressure(Systolic BP: r2=0.688, Diastolic BP: r2=0.722, Spearman rank test). Conclusion : The high serum concentration of VEGF is thought to be important in the development or pathophysiologic mechanism of preeclampsia. In the next study, the prospective analysis will be necessary to identify whether serum concentration of VEGF is abnormally high in early gestational pregnant women who are destined to preeclampsia.

난소의 원발성 이행세포암

정희정 ( Hee Jung Jung ),조용균 ( Yong Kyoon Cho ),최훈 ( Hoon Choi ),고지경 ( Ji Kyung Ko ),김명환 ( Myoung Hwan Kim ),김복린 ( Bok Rin Kim ),신은아 ( Eun Ah Shin ) 대한산부인과학회 2008 Obstetrics & Gynecology Science Vol.51 No.10

Primary ovarian transitional cell carcinoma (TCC) is extremely rare type of tumor and resembles transitional cell carcinoma of the bladder. Primary ovarian TCC has been classified as a different subtype from malignant Brenner tumor for it`s histologic and clinical characteristics. It usually presents at an advanced stage .Though more aggressive than malignant Brenner tumor, it shows more favorable prognosis because of better response to the chemotherapy than other epithelial ovarian carcinomas. We experienced a case of primary ovarian transitional cell carcinoma in a premenopausal woman who underwent staging operation and chemotherapeutic treatment, and herein report the case with a brief review of related literatures.

질식 분만된 조산아에서 아프가 점수 , 제대 동맥혈 가스분석의 임상적 의의

박지용(Ji Yong Park),정진훈(Jin Hoon Chung),박교훈(Kyo Hoon Park),조용균(Yong Kyoon Cho),최훈(Hoon Choi),김복린(Bok Rin Kim),이홍균(Hong Kyoon Lee),고수진(Su Jin Ko),서정식(Joung Sik Seo),유태환(Tae Hwan Yoo) 대한산부인과학회 1998 Obstetrics & Gynecology Science Vol.41 No.11

Objective: The Apgar score has long been used to determining birth asphyxia and assessing early neonatal status and long-term outcome. Unfortunately, some components of this system depend upon subjective interpretation. Also, although, low Apgar score, Most of newborns are relatively healthy. The objective of our studt is attempt to assure the linical significance of Apgar score and umbilical cord blood gas analysis on assessing status of uncomplicated preterm infants delivered vaginally. Methods: The present study was performed in attempt to compare umbilical arterial blood gas values for uncomplicated preterm infants delivered vaginally with low 1 and 5 minutes Apgar score (<7) with those for term or preterm infant with normal 1 and 5 minutes score (>7), each other, The present study included 82 uncomplicated term infants delivered vaginally and 24 preterm infants. Inclusion criteria of our study is as follows: 1) Singleton neonate with vertex presentation, 2) No congenital malformation, 3) Infants whose mother had no obstetrical and medical complications, 4) Immediately after delivery, umbilical arterial blood was sampled, before first breathing of neonate, 5) Infants applied Apgar score at I minute and again 5 minutes after birth, and 6) Infants whose mothers gestational age was estimated by ultrasonography during first-trimester of pregnancy. The statistical analysis was performed by Mann-Whitney U test and Fishers exact test. Results: 1) There was no significant difference in umbilical arterial blood gas values between uncomplicated preterm infants delivered vaginally with low 1 and 5 minutes Apgar score (<7) and term infants with normal score (>7). 2) There was no significant difference in umbilical arterial blood gas values between uncomplicated preterm infants delivered vaginally with low 1 and 5 minutes Apgar score (<7) and preterm infants with normal score (>7). 3) There was significant difference in frequency of lower Apgar score (<7) between term (2%[2/82]) and preterm infants (38%[9/24]), but not in frequency of acidemia (defined as less than pH 7.2) (28%[23/82] Vs 33%[8/24]). Conclusion: The Apgar score is not a reliable indieator of well-being in preterm neonate. We recommend umbilical arterial blood sampling at delivery of preterm infant with low Apgar score, because umbilical cord blood gas indices on objective means of assessing birth status of the newbarn and more useful than Apgar score in ruling out birth asphyxia.

태반조기박리가 동반된 임신성 고혈압 임산부와 정상혈압 임산부에서의 주산기 예후에 대한 비교 분석

박지용(Ji Yong Park),정진훈(Jin Hoon Chung),조용균(Yong Kyoon Cho),최훈(Hoon Choi),김복린(Bok Rin Kim),이홍균(Hong Kyoon Lee),유태환(Tae Hwan Yoo),고수진(Soo Jin Ko),박교훈(Gyo Hoon Park),서정식(Jeong Sik Seo) 대한산부인과학회 1998 Obstetrics & Gynecology Science Vol.41 No.11

Objective: The objective of this study was to compare perinatal outcomes of pregnancy-induced hypertensive and normotensive women experiencing abruptio placentae, Our hypothesis is that pregnancy-induced hypertensive women have a less favorable perinatal outcome than do normotensive women. Methods: Women with the diagnosis of abruptio placentae delivered between August 1,1989 and December 1,1996, composed the study group (n-92) in this case-control study. The women with abruptio placentae were divided according to their hypertensive (n 37) or normotensive (n 55) status. Maternal and neonatal medical records were reviewed and abstracted for demographic variables, antepartum complications, delivery route, abruptio placentae grade, neonatal gender, birth weight, Apgar score and perinatal mortality. We compared these perinatal outcome variables between the pregnancy-induced hypertensive and normotensive pregnant women. Results: The incidence of abruptio placentae was 0.35%. The two groups of woman wne similar with regard to age and parity. Abruptio placentae grades 2 occurred more often in hypertensive women (P=0.0053). Pregnancy-inducedhypertensive women were similar to normotensive women with regard to antenatal complications. The mean gestational age of delivery, delivery route, neonatal weight and sex were similar between two groups of women. Neonates from pregnancy-induced hypertensive women were no more likely to have low 1 and 5-minute Apgar score or to die than those from normotensive women. Statistical analysis was performed with two-tailed independent t-test and Kruskal-Wallis analysis. Conclusion: Although pregnancy-induced hypertensive women experiencing abruptio placentae are more likely to have grade 2 abruptio placentae with fetal distress, the overall perinatal outcome was not significantly different from that of normotensive women experiencing abruptio placentae.

분만 전 후 심장근육병증 환자의 임상적 특징과 예후

양용혁 ( Yong Hyuk Yang ),이가영 ( Ka Young Lee ),황희정 ( Hee Jung Hwang ),조용균 ( Yong Kyoon Cho ),김복린 ( Bok Rin Kim ),최훈 ( Hoon Choi ),이철민 ( Chul Min Lee ),고지경 ( Ji Kyung Ko ) 대한산부인과학회 2006 Obstetrics & Gynecology Science Vol.49 No.10

Objective: To examine clinical characteristics and risk factors and to assess prognosis of peripartum cardiomyopathy (PPCM). Methods: We retrospectively reviewed the medical records of 10 patients with confirmed PPCM by clinical symptoms and echocardiography, who delivered between January 1995 and December 2005 at our Hospital. Clinical and serial echocardiographic data of these patients were collected. Results: Mean maternal age at the time of diagnosis was 28.8±3.2 years and the mean gestational age was 37(+3)±4 weeks. Common associated conditions were nulliparity (90%), cesarean delivery (70%), anemia (70%), preeclampsia (60%), transfusion before diagnosis (40%), twin pregnancy (30%). At the time of diagnosis, the mean left ventricular ejection fraction (EF) was 42.84±9.69%, fractional shortening (FS) was 23.41±5.49%, and left ventricular end diastolic dimension (LVEDD) was 5.58±0.55 ㎝/㎡. Normalization of left ventricular function occurred in 8 patients (80%). After recovery of the left ventricular function, mean EF was 61.41±4.21%, FS was 34.08±3.26%, and LVEDD was 4.68±0.76 ㎝/㎡. Incidence of PPCM was 1 in 2455 pregnancies, and maternal mortality was 12.5% in 10 months follow-up. Conclusion: The risk of PPCM may increase in puerperal women with rapid dramatic hemodynamic change. Echocardiography may provide significant prognostic information.

한국인 임신성 고혈압 임부에서 factor V Leiden 염기변이에 관한 연구

조용균 ( Yong Kyoon Cho ),고지경 ( Ji Kyung Ko ),이철민 ( Chul Min Lee ),최훈 ( Hoon Choi ),김복린 ( Bok Rin Kim ),이홍균 ( Hong Kyoon Lee ) 대한산부인과학회 2005 Obstetrics & Gynecology Science Vol.48 No.4