Estrogen receptor 1, Glutathione S-transferase P1, Glutathione S-transferase M1, and Glutathione S-transferase T1 Genes with Dysmenorrhea in Korean Female Adolescents

Hee-Yeon Woo; Kye-Hyun Kim; Se-Won Lim

doi:10.3343/kjlm.2010.30.1.76

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Woo, Kim, and Lim: Estrogen receptor 1, Glutathione S-transferase P1, Glutathione S-transferase M1, and Glutathione S-transferase T1 Genes with Dysmenorrhea in Korean Female Adolescents

Original Article

Korean J Leg Med 2010;30(1):76-83.

Published online: 14 January 2010

DOI: https://doi.org/10.3343/kjlm.2010.30.1.76

Estrogen receptor 1, Glutathione S-transferase P1, Glutathione S-transferase M1, and Glutathione S-transferase T1 Genes with Dysmenorrhea in Korean Female Adolescents

Hee-Yeon Woo, M.D.¹, Kye-Hyun Kim, M.D.², Se-Won Lim, M.D.³

¹Departments of Laboratory Medicine, Obstetrics, Seoul, Korea

²Gynecology, and Psychiatry, Seoul, Korea

³Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

Corresponding author: Kye-Hyun Kim, M.D. Department of Obstetrics and Gynecology, Kangbuk Samsung Hospital, 108 Pyeong-dong, Jongno-gu, Seoul 110-746, Korea Tel: +82-2-2001-2457 Fax: +82-2-2001-2187 E-mail: khmd.kim@samsung.com

^∗ This study was supported by a Samsung Biomedical Research Institute Grant, #SBRI C-A7-301-1.

Revised 14 September 200913 November 2009 Accepted 20 November 2009

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background:

Dysmenorrhea is the most common gynecologic complaint among adolescent females. We investigated the association between genetic polymorphisms and dysmenorrhea.

Methods:

A total of 202 postmenarcheal Korean female adolescents 16-17 yr old participated in this study. Genotyping for glutathione S-transferase mu 1 (GSTM1), glutathione S-transferase theta 1 (GSTT1), glutathione S-transferase pi 1 (GSTP1), and estrogen receptor 1 (ESR1) was performed using PCR-based methods.

Results:

The PP+Pp genotype of the ESR1 gene was more frequent than pp genotypes in subjects with dysmenorrhea than in subjects without dysmenorrhea (odds ratio=2.440; 95% confidence interval, 1.036-5.753; P=0.040) using an unadjusted univariate logistic regression analysis. The relationship between dysmenorrhea and ESR1 gene polymorphisms remained significant after adjustment for premenstrual syndrome, years elapsed after menarche, and family history of dysmenorrhea. No significant difference was observed between subjects with dysmenorrhea and subjects without dysmenorrhea for polymorphisms of GSTM1, GSTT1, and GSTP1 genes.

Conclusions:

Our results suggest that ESR1 gene polymorphisms may be associated with dysmenorrhea.

Keywords: Adolescent, Dysmenorrhea, Estrogen receptor 1, Glutathione S-transferase, Polymorphism

REFERENCES

1.Andersch B., Milsom I. An epidemiologic study of young women with dysmenorrhea. Am J Obstet Gynecol. 1982. 144:655.

2.Dawood MY. Primary dysmenorrhea: advances in pathogenesis and management. Obstet Gynecol. 2006. 108:428–41.

3.Harel Z. Dysmenorrhea in adolescents. Ann NY Acad Sci. 2008. 1135:185–95.

4.Harlow SD., Park M. A longitudinal study of risk factors for the occurrence, duration and severity of menstrual cramps in a cohort of college women. Br J Obstet Gynaecol. 1996. 103:1134–42.

5.Parazzini F., Tozzi L., Mezzopane R., Luchini L., Marchini M., Fedele L. Cigarette smoking, alcohol consumption, and risk of primary dysmenorrhea. Epidemiology. 1994. 5:469–72.

6.Hirvonen A. Genetic factors in individual responses to environmental exposures. J Occup Environ Med. 1995. 37:37–43.

7.Lei L., Ye L., Liu H., Chen C., Fang Z., Wang L, et al. Passive smoking, cytochrome P450 gene polymorphisms and dysmenorrhea. Eur J Epidemiol. 2008. 23:475–81.

8.Wu D., Chen D., Liu X., Ni J., Jin Y., Xu X. Analysis on associations of cytochrome P450 1A1-Hinc II and glutathion S-transferase-theta with primary dysmenorrhea. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2001. 18:47–50.

9.Baxter SW., Thomas EJ., Campbell IG. GSTM1 null polymorphism and susceptibility to endometriosis and ovarian cancer. Carcinogenesis. 2001. 22:63–5.

10.Hur SE., Lee JY., Moon HS., Chung HW. Polymorphisms of the genes encoding the GSTM1, GSTT1, and GSTP1 in Korean women: no association with endometriosis. Mol Hum Reprod. 2005. 11:15–9.

11.Pelletier G., El-Alfy M. Immunocytochemical localization of estrogen receptors alpha and beta in the human reproductive organs. J Clin Endocrinol Metab. 2000. 85:4835–40.

12.Kitawaki J., Obayashi H., Ishihara H., Koshiba H., Kusuki I., Kado N, et al. Oestrogen receptor-alpha gene polymorphism is associated with endometriosis, adenomyosis and leiomyomata. Hum Reprod. 2001. 16:51–5.

13.Renner SP., Strick R., Oppelt P., Fasching PA., Engel S., Baumann R, et al. Evaluation of clinical parameters and estrogen receptor alpha gene polymorphisms for patients with endometriosis. Reproduction. 2006. 131:153–61.

14.Hu YF., Luscher B., Admon A., Mermod N., Tjian R. Transcription factor AP-4 contains multiple dimerization domains that regulate dimer specificity. Genes Dev. 1990. 4:1741–52.

15.Kim E., Hwang JY., Woo EK., Kim SS., Jo SA., Jo I. Body mass index cutoffs for underweight, overweight, and obesity in South Korean schoolgirls. Obes Res. 2005. 13:1510–4.

16.Yaich L., Dupont WD., Cavener DR., Parl FF. Analysis of the PvuII restriction fragment-length polymorphism and exon structure of the estrogen receptor gene in breast cancer and peripheral blood. Cancer Res. 1992. 52:77–83.

17.Lin DX., Tang YM., Peng Q., Lu SX., Ambrosone CB., Kadlubar FF. Susceptibility to esophageal cancer and genetic polymorphisms in glutathione S-transferases T1, P1, and M1 and cytochrome P450 2E1. Cancer Epidemiol Biomarkers Prev. 1998. 7:1013–8.

18.Harris R., Stubbins M., Forman D., Howard GC., Wolf CR. Identification of genetic polymorphisms at the glutathione-S-transferase Pi locus and association with susceptibility to bladder, testicular and prostate cancer. Carcinogenesis. 1997. 18:641–4.

19.Kim SH., Choi YM., Jun JK., Kim SH., Kim JG., Moon SY. Estrogen receptor dinucleotide repeat polymorphism is associated with minimal or mild endometriosis. Fertil Steril. 2005. 84:774–7.

20.Cho SH., Kim KD., Kim SR., Cho SH., Hwang YY. Adolescent menstrual disorders: Comparison between 1998 and 1998. Korean J Obstet Gynecol. 1999. 42:2043–7.

21.Kim HO., Lim SW., Woo HY., Kim KH. Premenstrual syndrome and dysmenorrhea in Korean adolescent girls. Korean J Obstet Gynecol. 2008. 51:1322–9.

22.Jung HM., Kim YS. Factors affecting dysmenorrhea among adolescents. J Korean Acad Child Health Nurs. 2004. 10:196–204.

23.Wu D., Wang X., Chen D., Niu T., Ni J., Liu X, et al. Metabolic gene polymorphisms and risk of dysmenorrhea. Epidemiology. 2000. 11:648–53.

24.Pierzynski P., Swiatecka J., Oczeretko E., Laudanski P., Batra S., Laudanski T. Effect of short-term, low-dose treatment with tamoxifen in patients with primary dysmenorrhea. Gynecol Endocrinol. 2006. 22:698–703.

25.Kurabayashi T., Tomita M., Matsushita H., Yahata T., Honda A., Takakuwa K, et al. Association of vitamin D and estrogen receptor gene polymorphism with the effect of hormone replacement therapy on bone mineral density in Japanese women. Am J Obstet Gynecol. 1999. 180:1115–20.

26.Willing M., Sowers M., Aron D., Clark MK., Burns T., Bunten C, et al. Bone mineral density and its change in white women: estrogen and vitamin D receptor genotypes and their interaction. J Bone Miner Res. 1998. 13:695–705.

27.Weel AE., Uitterlinden AG., Westendorp IC., Burger H., Schuit SC., Hofman A, et al. Estrogen receptor polymorphism predicts the onset of natural and surgical menopause. J Clin Endocrinol Metab. 1999. 84:3146–50.

28.Georgiou I., Syrrou M., Bouba I., Dalkalitsis N., Paschopoulos M., Navrozoglou I, et al. Association of estrogen receptor gene polymorphisms with endometriosis. Fertil Steril. 1999. 72:164–6.

29.Kitawaki J., Noguchi T., Amatsu T., Maeda K., Tsukamoto K., Yamamoto T, et al. Expression of aromatase cytochrome P450 protein and messenger ribonucleic acid in human endometriotic and adenomyotic tissues but not in normal endometrium. Biol Reprod. 1997. 57:514–9.

30.Wang Z., Yoshida S., Negoro K., Kennedy S., Barlow D., Maruo T. Polymorphisms in the estrogen receptor beta gene but not estrogen receptor alpha gene affect the risk of developing endometriosis in a Japanese population. Fertil Steril. 2004. 81:1650–6.

31.Lin J., Zhang X., Qian Y., Ye Y., Shi Y., Xu K, et al. Glutathione S-transferase M1 and T1 genotypes and endometriosis risk: a case-controlled study. Chin Med J. 2003. 116:777–80.

32.Kihara M., Kihara M., Noda K. Lung cancer risk of the GSTM1 null genotype is enhanced in the presence of the GSTP1 mutated genotype in male Japanese smokers. Cancer Lett. 1999. 137:53–60.

33.Shin SY., Lee YY., Yang SY., Yoon BK., Bae D., Choi D. Characteristics of menstruation-related problems for adolescents and premarital women in Korea. Eur J Obstet Gynecol Reprod Biol. 2005. 121:236–42.

34.Dawood MY. Dysmenorrhea. J Reprod Med. 1985. 30:154–67.

Table 1.

Primer sequences for PCR in this study

Gene	Primer sequence	PCR product (bp)
ESR1	(F) 5′-TTTCACGCAGTCTGGAGTTG-3′	496
	(R) 5′-ACCACACTCAGGGTCTCTGG-3′
GSTM1	(F) 5′-GAACTCCCTGAAAAGCTAAAGC-3′	219
	(R) 5′-GTTGGGCTCAAATATACGGTGG-3′
GSTT1	(F) 5′-TCACCGGATCATGGCCAGCA-3′	459
	(R) 5′-TTCCTTACTGGTCCTCACATCTC-3′
GSTP1	(F) 5′-ACCCCAGGGCTCTATGGGAA-3′	176
	(R) 5′-TGAGGGCACAAGAAGCCCCT-3′

Table 2.

Characteristics of participants (N=202)

Factors	Number (%)
Body mass index (kg/m²)
<18.20	26 (12.9)
18.20-22.69	135 (66.8)
22.70-24.67	22 (10.9)
≥24.68	19 (9.4)
Years elapsed after menarche
<2 yr	55 (27.2)
≥2 yr	147 (72.8)
Menstrual cycle
Regular	132 (65.3)
Irregular	70 (34.7)
Menstrual duration
Normal	171 (84.7)
Abnormal	28 (13.9)
Pre-menstrual syndrome
Absent	65 (32.2)
Present	137 (67.8)
Dysmenorrhea
Absent	30 (14.9)
Present	172 (85.1)
Family history of dysmenorrhea
Absent	70 (34.7)
Present	122 (60.4)
Smoking
No	200 (99.0)
Yes	2 (1.0)
Alcohol intake
No	190 (94.1)
Yes	12 (5.9)

Table 3.

Association between genotypes of ESR1, GSTM1, GSTP1, and GSTT1 genes and dysmenorrhea among 202 Korean female adolescents

Genotypes	N of group without dysmenorrhea (%)	N of group with dysmenorrhea (%)	Odds ratio (95% CI, P value∗)	Adjusted odds ratio^† (95% CI, Pvalue∗)
ESR1 genotypes
Dominant model
PP & Pp	15 (50.0)	122 (70.9)	2.440 (1.036-5.753, 0.040)	3.381 (1.393-8.209, 0.007)
pp	15 (50.0)	50 (29.1)	1.0	1.0
Recessive model
PP	5 (16.7)	35 (20.3)	1.277 (0.456-3.576, 0.641)	1.470 (0.492-4.392, 0.490)
Pp & pp	25 (83.3)	137 (79.7)	1.0	1.0
GSTM1
Present	11 (36.7)	82 (47.7)	1.0	ND
Null	19 (63.3)	90 (52.3)	0.599 (0.262-1.373, 0.226)
GSTP1
Ile/Ile	23 (76.7)	112 (65.1)	1.0	ND
Ile/Val	6 (20.0)	56 (32.6)	1.953 (0.737-5.174, 0.178)
Val/Val	1 (3.3)	4 (2.3)	0.420 (0.040-4.414, 0.469)
GSTT1
Present	16 (53.3)	81 (47.1)	1.0	ND
Null	14 (46.7)	91 (52.9)	1.322 (0.593-2.948, 0.495)

^∗ Pvalue <0.05 is statistically significant;

^† Odds ratios analyzed after adjusting for PMS, years elapsed after menarche, and family history of dysmenorrhea. Abbreviations: ND, not done; CI, confidence interval.

Table 4.

Association between combined genotype subgroups and dysmenorrhea

N of high-risk genotypes	Genes				N (%∗)	Odds ratio	95% CI	P value^†
N of high-risk genotypes	ESR1	GSTM1	GSTP1	GSTT1	N (%∗)	Odds ratio	95% CI	P value^†
0	pp	Present	ile/ile, ile/val	Present	17 (8.4)	1.0	0.469-6.961	0.389
1	PP, Pp	Present	ile/ile, ile/val	Present	55 (27.2)	1.808
	pp	Absent	ile/ile, ile/val	Present
	pp	Present	val/val	Present
	pp	Present	ile/ile, ile/val	Absent
2	PP, Pp	Absent	ile/ile, ile/val	Present	90 (44.6)	1.822	0.514-6.460	0.353
	PP, Pp	Present	val/val	Present
	PP, Pp	Present	ile/ile, ile/val	Absent
	pp	Absent	val/val	Present
	pp	Absent	ile/ile, ile/val	Absent
	pp	Present	val/val	Absent
3	PP, Pp	Absent	val/val	Present	40 (19.8)	2.154	0.500-9.282	0.303
	PP, Pp	Absent	ile/ile, ile/val	Absent
	PP, Pp	Present	val/val	Absent
	pp	Absent	val/val	Absent
4	PP, Pp	Absent	val/val	Absent	0 (0)	-	-	-

^∗ Proportion of subjects with dysmenorrhea among subjects with each genotype;

^† P value <0.05 is statistically significant.

Abbreviations: CI, confidence interval.

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