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[6] Frydman R, Lelaidier C, Baton-Saint-Mleux C, Fernandez VM, Vial H, Bourget P. Labor induction in women at term with mifepristone (RU 486): a double-blind, randomized, placebo-controlled study. Obstet Gynecol 1992;80(6):972–5. [7] Kapp N, Borgatta L, Stubblefield P, Vragovic O, Moreno N. Mifepristone in secondtrimester medical abortion: a randomized controlled trial. Obstet Gynecol 2007;110(6): 1304–10. [8] Goldberg AB, Greenberg MB, Darney PD. Misoprostol and pregnancy. New Engl J Med 2001;344(1):38–47.
[9] Saha S, Bal R, Ghosh S, Krishnamurthy P. Medical abortion in late second trimester- -a comparative study with misoprostol through vaginal versus through oral followed by vaginal route. J Indian Med Assoc 2006;104(2):81–2. [10] Wong KS, Ngai CS, Chan KS, Tang LC, Ho PC. Termination of second trimester pregnancy with gemeprost and misoprostol: a randomized double-blind placebo controlled trial. Contraception 1996;54(1):23–5.
0020-7292/$ – see front matter © 2009 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijgo.2009.03.005
Acetylcholinesterase gene polymorphism and recurrent pregnancy loss Farah Parveen a, Gaurav Tripathi a, Bhanumati Singh b, Rehan M. Faridi a, Suraksha Agrawal a,⁎ a b
Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, UP, India Department of Biotechnology, Bundelkhand University, Jhansi, UP, India
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Article history: Received 28 November 2008 Received in revised form 16 January 2009 Accepted 9 February 2009 Keywords: Acetylcholinesterase gene Insertion/deletion polymorphism Recurrent pregnancy loss Renin-angiotensin system
Recurrent pregnancy loss affects 0.5% to 2% of pregnant women, and is defined as at least 3 consecutive pregnancy losses before 24 weeks of gestation [1]. At least 2% of women of reproductive age experience 2 or more consecutive losses, and approximately 1% experience 3 or more. The causes of recurrent pregnancy loss are multifactorial, but the renin-angiotensin system, which occupies a key position in the maintenance of proper balance between vasoconstriction and vasodilatation, appears to play an important role in uteroplacental circulation and fetoplacental development. The enzyme acetylcholinesterase converts angiotensin I to angiotensin II, which has vasoconstrictor properties and consequently participates in vascular tone regulation [2]. Changes in the concentration of angiotensin II may affect the regulation of placental circulation. Spiral arteries undergo remodeling during pregnancy and the renin-angiotensin system may act as one of the mediators during this process [3]. The D allele of the insertion/deletion (I/D) polymorphism of the ACHE gene is associated with greater serum acetylcholinesterase activity, and is associated with phenotypic variance in serum enzyme levels [2]. The DD genotype is associated with the highest increase in circulating and tissue enzyme level and activity, which makes it a risk factor for recurrent pregnancy loss and a predictor of adverse pregnancy outcome for women with a history of pre-
⁎ Corresponding author. Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow (UP) 226014 India. Tel.: +91 522 668004 8x2338; fax: +91 522 6680973/6680017. E-mail address:
[email protected] (S. Agrawal).
eclampsia [2]. The present study examined the distribution of ACHE genotypes I and D in women from northern India who had experienced recurrent pregnancy loss. A group of 200 women who had experienced recurrent pregnancy loss at 24 weeks or less (171 had 3 or more losses, 26 had 5 or more losses, and 3 had 7 or more losses) was compared with an ethnically similar group of 300 women with a history of at least 2 live births and no history of pregnancy loss. Exclusion criteria were smoking and alcohol consumption. The study was approved by the institutional ethics committee and written informed consent was obtained from all participants. For genotyping, we used the protocol proposed by Fatini et al. [4]. The frequency distributions of the alleles within each group were compared between the groups by the Fisher exact test with the Bonferroni correction. P b 0.05 was considered statistically significant and odds ratios (ORs) with 95% confidence intervals were calculated. The mean± SD age in the study and control group was 28.4 ± 5.9 years and 31.9± 7.3 years, and the body mass index (calculated as weight in kilograms divided by height in meters squared) was 23.3± 4.1 and 23.9 ± 3.5. The differences between the groups were not significant. The mean number of pregnancy losses in the study group was 4 (range, 3–7). The genotype and allelic distribution in both groups is shown in Table 1. Both groups were in Hardy-Weinberg equilibrium. The distribution of the of DD and II genotypes was significantly different in the 2 groups (OR, 2.69; 95% CI, 1.66–4.37; P b 0.001). Highly significant differences observed between controls and patients at the genotypic level were also observed at the allelic level (OR, 1.71; 95% CI, 1.32–2.21; P b 0.001). We compared allele carriage frequency and found the frequency of the I and D alleles to be statistically different in the study and control groups (OR, 1.43; 95% CI, 1.06–1.94; P = 0.03). We evaluated the potential role of ACHE genotype as a predictor of recurrent pregnancy loss. Since the ACHE gene shows a wide diversity, a detailed analysis of polymorphism in renin-angiotensin system genes may be crucial to understand the mechanisms underlying initiation and progression of pregnancy loss. Recently, several studies have reported an association between ACHE polymorphism and the development and severity of various conditions, including end-stage renal disease, pregnancy-induced hypertension, and recurrence of adverse pregnancy outcomes in women with a history of pre-eclampsia [4]. The present study found that, in northern India, women homozygous for the DD allele of the ACHE gene were at high risk for recurrent pregnancy loss (OR, 2.69). Our results are similar to those of a study
BRIEF COMMUNICATIONS Table 1 Distribution of ACHE I/D genotype, allele frequency, and allele carriage frequency in the study participantsa. Genotype
Patients (n = 200)
Genotype frequency II 65 (32.5) ID 85 (42.5) DD 50 (25.0) Allele frequency I 215 (53.75) D 185 (46.25) Allele carriage frequency I allele carriage 150 (75.0) D allele carriage 135 (67.5)
Controls (n = 300)
P value
OR (95% CI)
132 (44.0) 135 (45.0) 33 (11.0)
0.0130 0.65 b 0.001
0.61 (0.42-0.89) 0.91 (0.63–1.29) 2.69 (1.66–4.37)
399 (66.5) 201 (33.5)
b 0.001
1.71 (1.32–2.21)
267 (89.0) 168 (56.0)
0.03 0.03
0.69 (0.52–0.95) 1.43 (1.06–1.94)
Abbreviations: CI, confidence interval; OR, odds ratio. a Values are given as number (percentage) unless otherwise indicated.
conducted on white women, which reported a near 3-fold increase in the risk of pregnancy loss for women with the DD genotype [5]. Of the polymorphism occurring in renin-angiotensin system genes, such as the angiotensin (AGT), angiotensin II type-1 receptor (AGTR1), renin (REN), and ACHE genes, the I/D polymorphism of the ACHE gene has been reported as a crucial determinant. If the I allele is found to be homozygous it could decrease the concentration of ACHE and hence decrease the rate of bradykinin inactivation in the placenta. This is crucial for vessel permeability and modulation of inflammatory reaction, thus provoking premature pregnancy loss [6]. On the other
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hand, the DD genotype increases acetylcholinesterase plasma concentration (more angiotensin I is converted into angiotensin II) and inactivation of bradykinin, and plays a key role in the origin and progression of endothelial dysfunction and vasoconstriction [2,7]. To conclude, our findings clearly establish an association between homozygosity for the DD allele of the ACHE gene and risk for recurrent pregnancy loss in women from northern India. References [1] Wilcox AJ, Weinberg CR, O'Connor JF, Baird DD, Schlatterer JP, Canfield RE, et al. Incidence of early loss of pregnancy. N Engl J Med 1988;319(4):189–94. [2] Tamura T, Johanning GL, Goldenberg RL, Johnston KE, DuBard MB. Effect of angiotensin-converting enzyme gene polymorphism on pregnancy outcome, enzyme activity, and zinc concentration. Obstet Gynecol 1996;88(4 Pt 1):497–502. [3] Mello G, Paretti E, Gensini F, Sticchi E, Mecacci F, Scarselli G, et al. Maternal–fetal flow, negative events, and preeclampsia: Role of ACE I/D polymorphism. Hypertension 2003;41:932–7. [4] Fatini C, Gensini F, Battaglini B, Prisco D, Cellai AP, Fedi S, et al. Angiotensinconverting enzyme DD genotype, angiotensin type 1 receptor CC genotype, and hyperhomocysteinemia increase first-trimester fetal-loss susceptibility. Blood Coagul Fibrinolysis 2000;11:657–62. [5] Dossenbach-Glaninger A, van Trotsenburg M, Schneider B, Oberkanins C, Hopmeier P. ACE I/D polymorphism and recurrent first trimester pregnancy loss: interaction with SERPINE1 4G/5G and F13 Val34Leu polymorphisms. Br J Haematol 2008;141(2):269–71. [6] Bespalova ON, Ivaschenko TE, Tarasenko OA, Demin GS, Ajlamazjan EK, Baranov VS. The angiotensin-converting enzyme gene polymorphism is associated with pregnancy miscarriage and placental insufficiency. BJMG 2007;10(1):3–8. [7] Perticone F, Ceravolo R, Maio R, Ventura R, Zingone A, Perrotti N, Mattioli PL. Angiotensin-converting enzyme gene polymorphism is associated with endothelium-dependent vasodilation in never-treated hypertensive patients. Hypertension 1998;31(4):900–5.
0020-7292/$ – see front matter © 2009 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijgo.2009.02.005
Long-term follow-up of a peer-led HIV/AIDS prevention program for married women in rural China Hang Hong a, Guo-Ping Ji b, Dong-Qing Ye a,⁎ a b
Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China Anhui Province Center for Disease Control and Prevention, Hefei, China
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Article history: Received 2 January 2009 Received in revised form 21 January 2009 Accepted 6 February 2009 Keywords: China Follow-up HIV/AIDS Long-term effects
Women are infected with HIV at increasing rates worldwide, and the incidence of new AIDS cases has been rising faster for women than
⁎ Corresponding author. Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032 China. Tel.: +86 551 5167726; fax: +86 551 5161171. E-mail addresses:
[email protected],
[email protected] (D.-Q. Ye).
for men [1]. In China, rural married women may become infected with HIV and other sexually transmitted infections (STIs) when their husbands return home after working in cities. Studies have demonstrated that many married rural women know little about condom use or STIs, and that their low level of knowledge puts them at risk [2]. Since HIV is mainly sexually transmitted and there is neither an effective vaccine nor a cure for HIV/AIDS [3], the most important way to control HIV/AIDS is to decrease high-risk sexual behavior by improving women's HIV/AIDS-related knowledge and attitudes. In 2007 and 2008, we conducted a follow-up study with 737 married women in North Anhui, China, to evaluate the long-term effects of a peer education program for married women. Multistage randomized cluster sampling was used. Clusters for each of 2 Anhui counties were randomly selected from clusters used in a previous study [4]. The questionnaire was designed carefully and consisted of queries about individual sociodemographic characteristics; 34 items regarding knowledge about reproductive health, HIV/AIDS, and STIs; and 10 items regarding attitudes toward people living with HIV/AIDS, premarital and extramarital sex, and condom use during sexual intercourse. The appropriate answer was credited with a score of 1 and an incorrect answer with a score of 0 for each response, and the sum of all scores was converted into
