한국여성에서 자간전증과 peroxisome proliferator-activated receptor-γ, methylenetetrahydrofolate reductase 유전자 다형성의 연관성

이소현 ( So Hyun Lee ),박보현 ( Bo Hyun Park ),박미혜 ( Mi Hye Park ),박혜숙 ( Hye Sook Park ),전선희 ( Sun Hee Chun ),안정자 ( Jung Ja Ahn ),류현미 ( Hyun Mee Ryu ),이광수 ( Kwang Soo Lee ),박현영 ( Hyun Young Park ),김영주 ( You 대한산부인과학회 2007 Obstetrics & Gynecology Science Vol.50 No.4

목적: 자간전증의 발병기전에 관여할 것으로 예측되는 PPARγ와 MTHFR 유전자의 단일염기다형성 및 일배체형과 한국인에서 자간전증의 연관성을 분석하고자 하였다. 연구 방법: 자간전증 환자 226명과 대조군 235명을 대상으로 하여 말초혈액검체에서 DNA를 추출하였고, PPARγ(-796A>G, P12A (C>G), H447H (161C>T)), MTHFR (A222V (677C>T), E429A (1298A>C), R594Q (1793G>A)) 유전자의 단일염기다형성의 유전자형은 SNaPShot assay kit를 이용한 single base primer extension assay로 분석하였다. 결과는 Student`s t-test, 카이제곱검정, 선형회귀분석으로 분석하였고, 일배체형 분석은 Haploview 3.2 version을 이용하여 수행하였다. 결과: 대상 환자들에서 PPARγ, MTHFR 유전자의 대립유전자 빈도 및 유전자형 빈도는 환자군과 대조군 간에 유의한 차이가 없었고 (p>0.05), PPARγ와 MTHFR의 단일염기다형성들의 유전자형은 자간전증 위험에 있어 유의한 차이가 없었다(p>0.05). PPARγ과 MTHFR 유전자의 단일염기다형성들 중 MTHFR 유전자의 3가지 단일염기다형성 677C>T, 1298A>C, 1793G>A 사이에 서로 강한 연관불균형을 보였으나 (Lod score>2.0), MTHFR 유전자의 TAG, CAG, CCA, CCG 일배체형의 유전자형의 분포는 환자군과 대조군 간에 유의한 차이가 없었고 (p>0.05) 자간전증 위험에 있어 통계적으로 유의한 차이가 없었다 (p>0.05). 결론: 이상의 결과를 통해 한국인에서 PPARγ과 MTHFR의 유전자다형성은 자간전증과 연관성이 없었고 이들의 일배체형도 연관성이 없었다. Objective: To investigate whether polymorphisms of genes encoding peroxisome proliferator-activated receptor-γ (PPARγ) and methylenetetrahydrofolate reductase (MTHFR) are associated with preeclmapsia in Korean women and also to demonstrate whether there is any haplotypic association between preeclampsia and those genes. Methods: DNA was extracted from whole blood of 226 preeclampsia patients and 235 healthy pregnant women. The genotypes of SNPs in PPARγ (-796A>G, P12A (C>G), H447H (161C>T)) and MTHFR (A222V (677C>T), E429A (1298A>C), R594Q (1793G>A)) were analyzed by a single base primer extension assay using a SNaPShot assay kit. Results were analyzed with the Student`s t-test, Chi-square test, and Logistic regression analysis. Haplotype analyses were performed using Haploview 3.2 version. Results: There were no significant differences in genotype or allele frequencies of PPARγ and MTHFR gene polymorphisms between preeclampsia patients and controls (p>0.05). No increase in the risk of preeclampsia for those genes was observed under any model of inheritance. Among SNPs of the PPARγ, MTHFR genes, only SNPs in MTHFR gene (677C>T, 1298A>C, 1793G>A) were in a strong linkage disequilibrium with each other (Lod score>2.0), but there were no significant differences in genotype distribution of haplotypes of MTHFR gene (TAG, CAG, CCA, CCG) between preeclampsia patients and controls (p>0.05). No statistically significant associations were observed between any haplotypes of MTHFR gene and preeclampsia risk. Conclusion: This study suggest that SNPs in PPARγ and MTHFR gene were not associated with preeclampsia in Korean women, and its haplotypes were also not associated with preeclampsia.

산전 진단된 연골무발생증 제2형

최노미 ( Noh Mi Choi ),김문영 ( Moon Young Kim ),양재혁 ( Jae Hyug Yang ),류현미 ( Hyun Mee Ryu ),정진훈 ( Jin Hoon Chung ),최준식 ( June Seek Choi ),문민환 ( Min Hwan Moon ) 대한주산의학회 2009 Perinatology Vol.20 No.1

We present a case of achondrogenesis type II demonstrating increased nuchal translucency on the first trimester ultrasound, which was confirmed in the second trimester ultrasound. Achondrogenesis type II is characterized by micromelia, varied ossification of spine, an enlarged calvarium with normal ossification, variable shortening of the ribs, and lack of rib fractures. In this case, ultrasonographic examination in the second trimester revealed a normally ossified cranium with relatively short long bones and a mildly protuberant abdomen due to small thorax and scanty ossified vertebral bodies. All these findings were compatible with the diagnosis of achondrogenesis type II. We further confirmed the diagnosis of achondrogenesis type II with postmortem radiographic examination.

자궁내 일측 태아사망에 합병된 쌍태임신에 관한 임상적 연구

오정미 ( Jeong Mi Oh ),김은성 ( Eun Sung Kim ),한호원 ( Ho Won Han ),김문영 ( Mun Young Kim ),류현미 ( Hyun Mee Ryu ),김의숙 ( Eu Sook Kim ),최도영 ( Do Young Choi ) 대한주산의학회 1996 大韓周産醫學會雜誌 Vol.7 No.1

비정상 산과력을 가진 부부에서의 균형전좌형 염색체 보인자의 빈도 및 그 보인자들에서의 산전 세포유전학적 진단

박소연,강인수,류현미,전종영,이문희,김진미,최수경,Part, So-Yeon,Kang, Inn-Soo,Ryu, Hyun-Mee,Jun, Jong-Young,Lee, Moon-Hee,Kim, Jin-Mi,Choi, Soo-Kyung 대한생식의학회 1997 Clinical and Experimental Reproductive Medicine Vol.24 No.3

Cytogenetic analysis was performed in 1321 couples and 141 women with history of abnormal reproductive outcome during 1988-1996. The use of high resolution banding technique and fluorescence in situ hybridization (FISH) in the chromosome analysis has made the precise evaluation of chromosome aberrations. The prevalence of balanced chromosomal translocation carriers were 3.74% (104/2783 patients). 70 cases (2.52%) were reciprocal translocation carriers and 34 (1.22%) had Robertsonian translocations. Chromosome aberrations were more frequent in women (73 cases) than in men (31 cases). No phenotypical abnormalities were found in all carriers, but they experienced abnormal reproductive outcomes such as recurrent spontaneous abortions, anomalous offsprings or infertility problem. Prenatal diagnosis was carried out on 36 subsequent pregnancies in balanced translocation carriers. The fetal karyotypes showed that 12 cases (33%) were normal, 22 (61%) were balanced translocations, and two (6%) were unbalanced translocations. It is concluded that the prevalence of balanced chromosomal translocations in patients with abnormal reproductive outcome is higher than that of the normal population. Most of the fetal samples showed normal karyotypes or balanced translocations. Although the incidence of chromosomal imbalance in the fetuses was relatively low in prenatal diagnosis, individuals with balanced translocations are predisposed to abnormal offspring with partial trisomy or monosomy. Therefore we recommend that genetic counselling and cytogenetic prenatal diagnosis for translocation carriers have to be offered to prevent recurrent chromosomal abnormal babies.

태아 목덜미 투명대(Nuchal Translucency) 증가의 임상적 효용성

김문영 ( Moon Young Kim ),류현미 ( Hyun Mi Ryu ),김은성 ( Eun Sung Kim ),양재혁 ( Jae Hyuk Yang ),한정렬 ( Jung Yul Han ),한호원 ( Ho Won Han ),이경상 ( Kyung Sang Lee ),유시준 ( Shi Joon Yoo ),이영호 ( Young Ho Lee ) 대한주산의학회 1998 Perinatology Vol.9 No.4

형광직접보합법을 이용한 착상전 유전진단 기법의 최적화와 경험 축적에 의한 임신율의 향상

임천규,민동미,이형송,변혜경,박소연,류현미,김진영,궁미경,강인수,전진현,Lim, Chun-Kyu,Min, Dong-Mi,Lee, Hyoung-Song,Byun, Hye-Kyung,Park, So-Yeon,Ryu, Hyun-Mee,Kim, Jin-Young,Koong, Mi-Kyoung,Kang, Inn-Soo,Jun, Jin-Hyun 대한생식의학회 2004 Clinical and Experimental Reproductive Medicine Vol.31 No.1

Objectives: This study was performed to evaluate the laboratory system for successful PGD using fluorescence in situ hybridization (FISH) and the clinical outcome of PGD cycles in five years experiences. Methods: A total of 181 PGD-FISH cycles of 106 couples were performed, and diagnosed chromosome normality in the preimplantation embryos. The laboratory and clinical data were classified by the following optimization steps, and statistically analyzed. Phase I: Blastomere biopsy with two kinds of pipettes, removal of cytoplasmic proteins without treatment of pepsin and culture of biopsied embryos with single medium; Phase II: Blatomere biopsy with single pipette, removal of cytoplasmic proteins with pepsin and culture of biopsied embryos with single medium; Phase III: Blastomere biopsy with single pipette, removal of cytoplasmic proteins with pepsin and culture of biopsied embryos with sequential media. Results: A total of 3, 209 oocytes were collected, and 83.8% (2, 212/2, 640) of fertilization rate was obtained by ICSI procedure. The successful blastomere biopsies were accomplished in 98.6% (2, 043/2, 071) of embryos, and the successful diagnosis rate of FISH was 94.7% (1, 935/ 2, 043) of blastomeres from overall data. Embryo transfers with normal embryos were conducted in 93.9% (170/181) of started cycles. There was no difference in the successful rate of biopsy and diagnosis among Phase I, II and III. However, the pregnancy rate per embryo transfer of Phase III (38.8%, 26/67) was significantly (p<0.05) higher than those of Phase I (13.9%, 5/36) and Phase II (14.9%, 10/67). Conclusions: The laboratory optimization and experience for the PGD with FISH procedure can increase the pregnancy rate to 38.8% in the human IVF-ET program. Our facility of PGD with FISH provides the great possibility to get a normal pregnancy for the concerned couples by chromosomal aberrations.

송변전 지리정보 시스템을 이용한 고압 송전선과 거주지 간 이격거리에 대한 인식 평가

옥민수(Minsu Ock),이무송(Moo-Song Lee),전보민(Bomin Jeon),김화정(Hwa Jung Kim),류현미(Hyun Mi Ryu),명성호(Sung-Ho Myung),민석원(Suk Won Min) 한국전자파학회 2015 한국전자파학회논문지 Vol.26 No.7

이번 연구에서는 송변전 지리정보 시스템(Transmission and substation Geographic Information System: TGIS)을 이용하여 일반인들이 판단한 고압 송전탑 및 송전선, 변전소와 거주지 간 거리 인식이 실측 거리와 일치하는지 확인해 보았다. 총 725명의 응답자 중 136명이 고압 송전탑 및 송전선, 변전소가 눈에 보이는 거리에 있다고 응답하였고, 이 중 114명이 TGIS로 분석할 수 있는 유효한 주소를 제공하였다. 114명 중 42명(36.8 %)은 실측 거리보다 인식 거리가 짧았으며, 15명 (13.2 %)은 인식 거리보다 실측 거리가 짧았다. 일반인들의 고압 송전탑 및 송전선, 변전소와 거주지 간 거리 예측의 타당도가 높지 않은 점을 바탕으로 했을 때, 이를 극저주파 전자기장 노출량의 대용물로 사용하는 것은 부적절할 것으로 보인다. The purpose of this study was to evaluate the perceived distance from home to high-voltage power lines using a transmission and substation geographic information system(TGIS). Of the 725, 136 respondents reported that high voltage power transmission tower, power lines or substation was within visual field range from home. Among them, 114 respondents reported valid address, which could be used in the analysis of TGIS. Forty two respondents(36.8 %) estimated that the power lines were closer and 15 respondents(13.2 %) estimated that they were farther than they actually were. Our current findings suggest that the reported distance from home to high-voltage power transmission towers, power lines, and substations cannot be used as a proxy for exposure to electromagnetic fields due to the low validity.

융모막 융모세포의 염색체분석에서 관찰된 태반 국한성 혼재현상

최수경 ( Soo Kyung Choi ),임선아 ( Son Ah Lim ),박소연 ( So Yeon Park ),김영미 ( Young Mi Kim ),김진미 ( Jin Mee Kim ),김문영 ( Moon Young Kim ),류현미 ( Hyun Mee Ryu ),전종영 ( Jong Young Jun ) 대한주산의학회 1996 大韓周産醫學會雜誌 Vol.7 No.2

계류유산 환자에서 자궁 경을 통한 유산아 관찰의 진단적 유용성에 관한 연구

양광문 ( Kwang Moon Yang ),차선화 ( Sun Hwa Cha ),김해숙 ( Hae Suk Kim ),김진영 ( Jin Young Kim ),김혜옥 ( Hye Ok Kim ),안현경 ( Hyun Kyong Ahn ),최준식 ( June Seek Choi ),류현미 ( Hyun Mee Ryu ),강인수 ( In Soo Kang ),궁미경 ( Mi 대한산부인과학회 2005 Obstetrics & Gynecology Science Vol.48 No.2

목적: 임상적으로 인지된 임신의 약 15-20%는 자연유산 되며, 이런 유산의 60-70%는 염색체 이상에 의한다. 하지만 이런 자연유산의 유산산물에 대한 발생학적 관점에서의 연구는 잘 알려지지 않았다. 본 연구에서 저자들은 계류유산에서 유산아의 해부학적 이상을 검사하는데 있어 자궁 경 검사를 이용한 유산아 관찰의 유용성에 대해 알아보고 유산아의 관찰소견과 염색체 검사의 결과를 비교, 분석하고자 하였다. 연구 방법: 2003년 8월 1일부터 2003년 Objective: Approximately 15-20% of all clinically recognized pregnancies result in spontaneous abortion and 60-70% of these are attributable to detectable chromosome abnormalities. Although the incidence of first trimester losses is high, spontaneous abor

산모의 다중예측 인자를 이용한 임신 합병증 예후에 관한 다변량분석

한인수(In Soo Han),한정열(Jung Yeol Han),고명인(Myong In Ko),최용관(Yong Kwan Choi),이홍복(Hong Bok Lee),양재혁(Jea Hyuk Yang),류현미(Hyun Mi Ryu),김문영(Moon Young Kim),김은성(Eun Sung Kim),한호원(Ho Won Han) 대한산부인과학회 1999 Obstetrics & Gynecology Science Vol.42 No.8

산모의 다중예측 인자를 이용한 임신 합병증 예후에 관한 다변량분석 목적: Maternal serum markers(AFP, uE3, hCG ), Unexplained down syndrome screen positive에 의한 태아예후를 비교하기위함. 연구방법: 1994년 3월부터 1996년 2월까지 임신 2기에 삼성제일병원을 방문하여 Triple marker test를 시행하고 본원에서 분만 기록이 있는 단태아 5,284례를 대 상으로 하였다. 각 산모 혈청 표지물질들은 radioimmunoassay kit를 이용하여 측정하였고 다운 증후군 스크린 양성은 α-software(Ver. 4.0)를 이용하여 산출하였다. 임신과 관련된 임신 합병증 예후의 기준은 조기태반 박리는 분만시 태반 소견을 기준으로 하였으며, 저체중아는 2500gm 미만, 만삭전 파수는 임신 37주 이전에 조기 양막 파수되는 경우로 하였다. 결과: 검사를 받은 산모의 평균 연령은 30±4.8세이며, 임신횟수는 평균 2.27, 출산횟수는 0.46이며, 검사를 시행한 평균 임신주수는 17.1주이었다. 저체중아는 357례(6.8%), 미숙아는 253례(4.8%), 전치태반은 108례(2.0%), 만삭전 파수는 68례(1.3%), 임신중독증은 66례(1.3%), 조기태반박리 24례(0.5%),자궁내 태아사망은 20례(0.4%)이었다. 이러한 임신 합병증 예후와 산모의 연령 AFP,hCG,uE3,그리고 Unexplained Down syndrome screen positive의 통계적 연관성에 관한 분석에서 35세 이상군은 조기태반 박리, 미숙아, 전치태반에서, AFP 2.0 이상군은 자궁내 태아사망, 저체중아, 임신중독증, 미성숙 조기 양수 파막, 미숙아에서, hCG 3.0 이상군은 자궁내 태아사망, 저체중아, 임신중독증, 미숙아, 전치태반에서, uE3 0.75 미만군에서는 자궁내 태아사망, 저체중아, 미숙아에서만, 그리고 unexplained Down syndrome screen positive에서는 조기태반 박리 , 자궁내 태아사망, 저체중아, 미숙아에서 통계적인 의미가 있었다. 또한 임신 합병증 예후와 관련된 혼란 변수를 조절하고 가장 영향력 있는 인자를 알기위해 multivariate logistic regression을 시행하였다. 자궁내 태아사망은 AFP 2.0 MoM이상, 저체중아는 AFP 2.0 MoM이상, hCG 3.0MoM이상, uE3 0.75 MoM 미만, 임신 중독증은 AFP 2.0 MoM이상, 미성숙 조기 양수 파막은 AFP 2.0 MoM이상, 미숙아는 AFP 2.0 MoM이상, 전치 태반은 35세 이상의 산모군과 hCG 3.0 MoM 이상군에서 P value 0.05 미만으로 통계적으로 의미있는 결과가 나왔으며, 조기태반 박리의 경우 35세 이상의 산모군에서만 P value 0.07이었다. 결론: 임신 합병증 예후를 예측하기위한 예측인자로서 산모의 고령 나이를 비롯해 산모혈청의 AFP, hCG, uE3과 Unexplained Down syndrome screen positive는 모두 다변량 분석에서 통계학적으로 의미가 있으며, 또한 다변량 분석에서는 증가된 AFP이 임신 합병증을 예측하는데 가장 신뢰성 있는 인자임을 알 수 있었다. Purpose : To evaluate a role as over 35 years, maternal serum markers, and a false positive screen for Down syndrome were the predictor of adverse pregnancy outcome. Materials and Methods : From Mar.1994, through Feb.1996, 5284 women were screened triple test to detect Down syndrome in the second trimester and were delivered Samsung Cheil hospital. The values of each maternal serum markers were measured with radioimmunoassay. And then, the screen positive of Down syndrome was calculated using α-software Version 4.0. The adverse outcome of the fetus and the mother included low birth weight(LBW) ( <2500gm), prematurity( <37 gestational weeks), placenta previa, preterm premature rupture of membranes(PPROM), pregnancy induced hypertension(PIH),abruptio placenta, and intrauterine fetal death(IUFD). The predictor markers included over 35years, elevated α-fetoprotein (AFP), elevated human chorionic gonadotropin(hCG), lowered unconjugated estriol (uE3), and a false positive screen for Down syndrome. Results : Mean age and mean gestational weeks in the study were 30±4.8 years and 17.1 weeks respectively. The adverse pregnancy outcomes were 357 LBW(6.8%), 253 prematurity(4.8%), 108 placenta previa(2.0%), 68 PPROM(1.3%), 66 PIH(1.3%), 24 abruptio placenta(0.5%), and 20 IUFD(0.4%). In univariate analysis, over 35 years was significantly associated with abruptio placenta, prematurity, and placenta previa, elevated MS-AFP( >2.0 MoM) associated with IUFD, LBW, PIH, prematurity, and PPROM , elevated MS-hCG (>3.0 MoM) associated with IUFD, LBW, PIH, prematurity, and placenta previa, lowered uE3 (<0.75) associated with IUFD, abruptio placenta, LBW, and prematurity.(P <0.05). In multivariate logistic regression analysis, IUFD was significantly associated with only elevated MS-AFP, LBW associated with elevated MS-AFP, elevated MS-hCG, and lowered uE3, PIH associated with only elevated MS-AFP, PPROM only elevated MS-AFP, prematurity only elevated MS-AFP, and placenta previa over 35 years, elevated MS-hCG.(P <0.05). However, abruptio placenta was not significantly associated with predictor markers.(P >0.05) Conclusions : Some predictors such as over 35 year, elevated hCG, lowered uE3, a false positive screen for Down syndrome were significantly associated with adverse pregnancy outcome. Also in multivariate analysis, we identified especially elevated AFP to be the most reliable predictor for adverse pregnancy outcome.