자궁내막증 환자에서 에스트로겐 수용체 유전자 Dinucleotide Repeat 다형성 양상 = Estrogen Receptor Dinucleotide Polymorphism in Patients with Endometriosis

국문 초록 (Abstract)

목적 : 한국 여성에서 에스트로겐 수용체 유전자의 dinucleotide repeat 다형성과 자궁내막증의 연관성에 대하여 조사하고자 하였다.
연구 방법 : 수술 소견 또는 조직검사상 자궁내막증으로 진단된 156명의 여성을 환자군으로 하였으며, 복강경 검사 또는 개복술을 시행하였으나 자궁내막증의 증거를 발견할 수 없었던 137명을 대조군으로 하였다. 이들에서 에스트로겐 수용체 유전자의 dinucleotide repeat 다형성 양상을 fluorescent PCR 및 gene scan analysis를 이용하여 조사하였다.
결과 : 대상인에서 총 16개의 에스트로겐 수용체 유전자의 dinucleotide repeat 다형성 대립유전자가 발견되었다 (12-27 repeats, 26 repeats는 없음). 자궁내막증 환자에서 대립유전자들 (allele)의 분포는 대조군와 유의한 차이가 없었다. 그러나 자궁내막증 환자들을 stage -I-II와 stage III-IV로 구분하여 분석하였을 때, 자궁내막증 stage I-II군 (51명)에서 낮은 반복횟수 (12-15 repeats)의 대립유전자들의 빈도는 대조군보다 유의하게 높았다 (67.6％ vs 52.9％, p=0.010 odds ratio=1.860). 반면 자궁내막증 stage III-IV군 (105명)에서 낮은 반복횟수 (12-15 repeats)의 대립유전자들의 빈도는 대조군와 차이가 없었다 (55.70％ vs 52.9％).
결론 : 한국 여성에서 에스트로겐 수용체 유전자의 dinucleotide repeat 다형성은 경증의 자궁내막증 발생과 연관이 있었다.

다국어 초록 (Multilingual Abstract)

Objective : To explore the association of the estrogen receptor dinucleotide repeat polymorphism with the risk of endometriosis. Design : Case-control study Methods : One hundred fifty-one women with surgically or histologically diagnosed endometriosis of stages I-IV (ASRM, 1997) were recruited, and 137 patients with no evidence of endometriosis by laparoscopy or laparotomy served as control. Dinucleotide repeat polymorphism of the estrogen receptor gene was assessed by fluorescent PCR with gene scan analysis. Allele frequencies of dinucleotide repeat polymorphism of the estrogen receptor gene were evaluated. Results : Fifteen alleles of the estrogen receptor dinucleotide repeat polymorphism were found in subjects: from 12 repeats to 27 repeats except 26 repeats. There was no statistically significant difference in the allele distribution of dinucleotide repeat polymorphism between patients with endometriosis and controls. However, patients with stage I or II endometriosis (n=51) showed a higher incidence of alleles with fewer (TA)n repeats (12-15 repeats) compared with controls (67.6％ vs 52.9％, p=0.010, odds ratio=18.860). Conclusion : These results suggest that dinucleotide repeat polymorphism of the estrogen receptor gene is associated with the risk of minimal or mild endometriosis in the Korean population.

참고문헌 (Reference)

1 "자궁내막증 환자에서 에스트로겐 수용체 유전자 PvuII 및 XbaI 다형성 양상" in press 2003

2 "Treatment of endometriosis with a potent agonist of gonadotropin-releasing hormone(nafarelin)" 44 : 583-588, 1985

3 "The relationship between laparoscopic disease, pelvic pain and infertility; an unbiased assessment" 74 : 57-62, 1997

4 "The protective effect of hormone-replacement therapy on fracture risk is modulated by estrogen receptor alpha genotype in early postmenopausal women" 15 : 2479-2486, 2000

5 "The familial risk of endometriosis" 72 : 560-564, 1993

6 "Serum oestradiol and oestrogen-receptor gene polymorphism are associated with bone mineral density independently of serum testosterone in normal males" 49 : 8039-, 1998

7 "Revised American Fertility Society classification of endometriosis:1985" 43 : 351-352, 1985

8 "PvuII polymorphisms of the estrogen receptor alpha and bone mineral density in healthy southern Chinese women" 66 : 405-408, 2000

9 "Possible involvement of arylamine N-acetyltransferase 2, glutathione S-transferases M1 and T1 genes in the development of endometriosis" 5 : 636-641, 1999

10 "Polymorphisms of the VDR, ER and COLIA1 genes and osteoporotic hip fracture in elderly postmenopausal women" 11 : 583-591, 2000

11 "Peritoneal endometriosis, ovarian endometriosis and adenomyotic nodules of the rectovaginal septum: a different histopathogenesis?" 6 : 203-209, 1997

12 "Ovarian steroid regulation of vascular endothelial growth factor in the human endometrium:implications for angiogenesis during the menstrual cycle and the pathogenesis of endometriosis" 81 : 3112-3118, 1996

13 "Oestrogen receptor-alpha gene polymorphism is associated with endometriosis, adenomyosis and leiomyomata" 16 : 51-55, 2001

14 "Nonassociation of estrogen receptor genotypes with bone mineral density and estrogen responsiveness to hormone replacement therapy in Korean postmenopausal women" 82 : 991-995, 1997

15 "No major effect of estrogen receptor gene polymorphisms on bone mineral density or bone loss in postmenopausal Danish women" 26 : 111-116, 2000

16 "Lack of an association of estrogen receptor alpha gene polymorphisms and transcriptional activity with Alzheimer disease" 57 : 236-240, 2000

17 "Interleukin-8 concentration in peritoneal fluid of patients with endometriosis and modulation of interleukin-8 expression in human mesothelial cells" 2 : 40-45, 1996

18 "Human oestrogen receptor cDNA: sequence, expression and homology to v-erb-A" 320 : 134-139, 1986

19 "Genetic association between rheumatoid arthritis and estrogen receptor microsatellite polymorphism" 27 : 1638-1642, 2000

20 "Family trait analysis:a case- control study of 43 women with endometriosis and their best friends" 154 : 596-601, 1986

21 "Familial endometriosis" 12 : 32-34, 1995

22 "Evidence of a linkage disequilibrium between polymorphisms in the human estrogen receptor alpha gene and their relationship to bone mass variation in postmenopausal Italian women" 9 : 2043-2050, 2000

23 "Estrogen receptor gene polymorphisms in patients with Alzheimer's disease, vascular dementia and alcohol-associated dementia" 11 : 119-122, 2000

24 "Estrogen receptor gene polymorphism in Japanese patients with multiple sclerosis" 179 : 70-75, 2000

25 "Estrogen receptor gene polymorphism and its association with clinicopathological manifestation of lupus nephritis" 17 : 266-269, 2000

26 "Estrogen receptor alpha gene polymorphisms and endometrial cancer risk" 21 : 623-627, 2000

27 "Estrogen receptor alpha dinucleotide repeat polymorphism in Japanese patients with autoimmune thyroid diseases" 1 : 1-7, 2000

28 "Endometriosis in monozygotic twins" 68 : 941-942, 1997

29 "Early postmenopausal bone loss is associated with PvuII estrogen receptor gene polymorphism in Finnish women:effect of hormone replacement therapy" 15 : 315-321, 2000

30 "ER beta:identification and characterization of a novel human estrogen receptor" 392 : 49-53, 1996

31 "Dinucleotide repeat polymorphism in the human estrogen receptor (ESR) gene" 1 : 354-, 1992

32 "Association of estrogen receptor gene polymorphisms with endometriosis" 72 : 164-166, 1999

33 "Association of bone mineral density with polymorphism of the estrogen receptor gene" 11 : 306-311, 1996

34 "Association of Estrogen Receptor Dinucleotide Repeat Polymorphism with Osteoporosis" 217 : 378-383, 1995

35 "Analysis of the PvuII restriction fragment-length polymorphism and exon structure of the estrogen receptor gene in breast cancer and peripheral blood" 52 : 77-83, 1992

36 "A TA repeat polymorphism in the estrogen receptor gene is associated with osteoporotic fractures but polymorphisms in the first exon and intron are not" 15 : 2222-2230, 2000