정신분열병 환자에서 G-protein β3 Subunit Gene (GNB3)의 C1429T 유전자의 다형성 = Polymorphisms of G-protein β3 Subunit Gene(GNB3) C1429T in Korean Schizophrenic Patients

국문 초록 (Abstract)

목적 : 본 연구는 정신 분열병과 관계있다고 알려진 GNB3 유전자 중, C1429T 유전자 다형성에 초점을 맞추어 정신분열병과 연관 관계를 알아보기 위하여 시행되었다.
방법 : DSM-IV 진단기준에 의해 진단된 정신분열병 환자군 100명과 정상 대조군 90명을 대상으로 하였다. C1429T 유전자형 판별을 위해 Restriction Fragment Length Enzyme(RFLP)을 이용한 Polymerase Chain Reaction(PCR)이 사용되었다.
결과 : 정신분열병 환자군에서 C1429T 유전자형의 분포는 CC 64(64.0%), CT 36(36.0%), TT 0(0.0%) 이었으며, 대립 유전자의 빈도는 C 164(82.0%), T 36(18.0%)이었다. 정상 대조군에서 C1429T 유전자형의 분포는 CC 60(66.7%), CT 24(26.7%), TT 6(6.7%) 이었으며 대립 유전자의 빈도는 C 144(80.0%), T 36(20.0%)이었다. 정신분열병 환자군과 대조군 간 C1429T 유전자형의 분포에서 통계적으로 의미 있는 차이를 보여주고 있었으나, 대립 유전자의 빈도에서는 차이는 유의미하지 않았다. 또한, 환자군을 성별, 정신과적 질병의 가족력, PANSS scale에 따른 증상 심각도 등의 변수에 따라 분류하였을 때도 유전자형의 분포와 대립 유전자의 빈도 차이는 유의미하지 않았다.
결론 : 이 연구의 결과는 한국인 정신분열병 환자들에서 GNB3/C1429T 유전자 다형성이 정신분열병의 병인과 관계가 있음을 보여준다. 가족-기초 비교 위험 연구와 정신분열병의 다른 임상적 변수들을 포함한 향후의 연구가 필요할 것이다.

다국어 초록 (Multilingual Abstract)

Objectives：This study aimed to investigate the association between polymorphisms of CNB3/C1429T and schizophrenia.
Methods：100patients with schizophrenia and 90controls were enrolled in the study. A polymerase chain reaction( PCR) with restriction fragment length enzyme(RFLP) was used to genotype the C1429T polymorphisms.
Results：1) In schizophrenic patients, genotype distributions of the GNB3/C1429T polymorphism were CC 64(64.0%), CT 36(36.0%) and TT 0(0.0%), and allele frequencies were C 164(82.0%), and T 36(18.0%). In normal control, genotype distributions of the GNB3/C1429T polymorphism were CC 60(66.7%), CT 24(26.7%) and TT 6(6.7%), and allele frequencies were C 144(80.0%), and T 36(20.0%). There were significant differences in the genotype frequencies of the GNB3/C1429T polymorphisms between the schizophrenia patients and the controls, while no significant differences in the alleic frequencies. 2) There were no difference in genotype distribution and allele frequencies of the GNB3/C1429T polymorphism, when patients were categorized by sex, family history of psychiatric disease, severity of symptom with PANSS scale.
Conclusions：These results suggest a GNB3/C1429T polymorphism is causally related to the pathogenesis of schizophrenia in the Korean population. Further study of GNB3/C1429T polymorphism should be needed, including family based association study and other clinical variations of schizophrenia.

목차 (Table of Contents)

• 서론
• 대상 및 방법
• 연구성적
• 고찰
• 요약
• 참고문헌

참고문헌 (Reference)

1 채정호, "정신장애의 신경생물학" 서울: 중앙문화사 29-30, 2005

2 김철응, "정신분열병 및 기타정신병" 서울: 중앙문화사 416-417, 2005

3 Siffert W, "Worldwide ethnic distribution of the G protein beta 3 subunit 825T allele and its association with obesity in Caucasian, Chinese, and Black African individuals" 10 : 1921-1930, 1999

4 Avissar S, "The role of G protein in the psychobiology and treatment of affective disorders and their integration with the neurotransmitter hypothesis" 1 : 148-153, 1999

5 Minoretti P, "The T393C polymorphism of the GNAS1 gene is associated with deficit schizophrenia in an Italian population sample" 397 (397): 159-163, 2006

6 Taymans JM, "Striatal gene expression of RGS2 and RGS4 is specifically mediated by dopamine D1 and D2 receptors: clues for RGS2 and RGS4 functions" 84 : 1118-1127, 2003

7 Manji HK, "Signal transduction pathways: Molecular targets for lithium's actions" 52 : 531-543, 1995

8 Hildebrandt JD, "Role of subunit diversity in signaling by heterotrimeric G proteins" 54 : 325-339, 1997

9 Birnbaurner I, "Receptor-effector coupling by G proteins" 163-24,

10 Suwazono Y, "G-protein beta 3 subunit polymorphism C1429T and low-density lipoprotein receptor-related protein 5 polymorphism A1330V are risk factors for hypercholesterolemia in Japanese males : a prospective study over 5 years" 55 (55): 751-757, 2006

11 Dishy V, "G-Protein beta(3) subunit 825C/T polymorphism is associated with weight gain during pregnancy" 13 : 241-242, 2003

12 Hegele RA, "G-Protein beta 3 subunit gene splice variant and body fat distribution in Nunavut Inuit" 9 : 972-977, 1999

13 Beige J, "G-Protein beta 3 subunit C825T variant and ambulatory blood pressure in essential hypertension" 33 : 1049-1051, 1999

14 Siffert W, "G-Protein beta 3 subunit 825T allele and hypertension" 5 : 47-53, 2003

15 Benjafield AV, "G-Protein beta 3 subunit gene (GNB3) variant in causation of essential hypertension" 32 : 1094-1097, 1998

16 Gilman AG, "G proteins transducers of receptor-generated signals" 615-49,

17 "G proteins implication for psychiatry" 746-60, amjpsychiatry1992;149

18 Dieter R, "G protein β3 Gene: structure, Promotor, and Additional Polymorphism" 36 : 33-41, 2000

19 Gutersohn A, "G Protein beta 3 subunit 825 TT genotype and post-pregnancy weight retention" 355 : 1240-1241, 2000

20 Zill P, "Evidence for an association between a G-protein beta3-gene variant with depression and response to antidepressant treatment" 26 (26): 1893-1897, 2000

21 Avissar S, "Elevated dopamine receptor-coupled G(s) protein measures in mononuclear leukocytes of patients with schizophrenia" 15 (15): 37-47, 2001

22 Wang HY, "Effects of lithium on receptor-mediated activation of G proteins in rat brain cortical membranes" 403-14, neuropsychopharmacology1999;38

23 Kleuss C, "Different beta-subunits determine G-protein interaction with transmembrane receptors" 358 : 424-426, 1992

24 Jarskog LF, "Cortical bcl-2 protein expression and apoptotic regulation in schizophrenia" 48 : 641-650, 2000

25 Willeit M, "C825T polymorphism in the G protein beta3-subunit gene is associated with seasonal affective disorder" 54 : 682-686, 2003

26 Kunugi H, "Association study of C825T polymorphism of the G-protein β3 subunit gene with schizophrenia and mood disorders" 109 : 213-218, 2002

27 Siffert W, "Association of a human G protein beta 3 subunit variant with hypertension" 18 : 45-48, 1998

28 Dong Y, "Association between the C825T polymorphism of the G protein beta 3 subunit gene and hypertension in blacks" 34 : 1193-1196, 1999

29 Schunkert H, "Association between a polymorphism in the G protein beta 3 subunit gene and lower renin and elevated diastolic blood pressure levels" 32 : 510-513, 1998

30 Hengstenberg C, "Association between a polymorphism in the G protein beta 3 subunit gene (GNB3) with arterial hypertension but not with myocardial infarction" 49 : 820-827, 2001

31 Chowdari KV, "Association and linkage analyses of RGS4 polymorphisms in schizophrenia" 11 : 1373-1380, 2002

32 Corson TW, "Association analysis of G-protein β3 subunit gene with altered Ca(2+) homeostasis in bipolar disorderAssociation analysis of G-protein β3 subunit gene with altered Ca(2+) homeostasis in bipolar disorder" 6 : 125-126, 2002

33 Jarskog LF, "Apoptotic mechanisms in the pathophysiology of schizophrenia" 29 : 846-858, 2005

34 Brand E, "An epidemiological study of blood pressure and metabolic phenotypes in relation to the Gbeta3 C825T polymorphism" 21 : 729-737, 2003