PDF herunterladen
CC BY 4.0 · Rev Bras Ginecol Obstet 2021; 43(11): 805-810
DOI: 10.1055/s-0041-1736342
Original Article
Obstetrics

Association Between PON1 (L55M and Q192R) Genetic Polymorphism and Recurrent Pregnancy Loss in North Indian Women Exposed to Pesticides

Associação entre o polimorfismo genético PON1 (L55M e Q192R) e a perda recorrente de gravidez em mulheres do norte da Índia expostas a pesticidas
Shyam Pyari Jaiswar 
1   Department of Obstetrics and Gynecology, King George's Medical University, Lucknow, Uttar Pradesh, India
,
Apala Priyadarshini 
1   Department of Obstetrics and Gynecology, King George's Medical University, Lucknow, Uttar Pradesh, India
,
Apurva Singh 
1   Department of Obstetrics and Gynecology, King George's Medical University, Lucknow, Uttar Pradesh, India
,
Mohd Kalim Ahmad 
2   Department of Biochemistry, KGMU, Lucknow, Uttar Pradesh, India
,
Sujata Deo 
1   Department of Obstetrics and Gynecology, King George's Medical University, Lucknow, Uttar Pradesh, India
,
Pushpa Sankhwar 
1   Department of Obstetrics and Gynecology, King George's Medical University, Lucknow, Uttar Pradesh, India
› Institutsangaben Funding/Acknowledgments The authors would like to thank UP-CST for the grant (CST/SERPD/D-2243).
› Weitere Informationen
   Lizenzen und Reprints

Abstract

Objective The aim of the present study was to examine the relation between the PON1 polymorphisms and recurrent pregnancy loss (RPL).

Methods In a cross-sectional study, blood samples were collected from 100 females. DNA was extracted and PON1 genotypes were determined by polymerase chain reaction (PCR) amplification.

Results Regarding PON1 L55M, the mutated allele (M) frequency was found in 70.5% in RPL and in 53.5% in controls; the M allele was significantly associated with an increased risk of RPL (adjusted odds ratio [ORadj] = 2.07; 95% confidence interval [CI]; p < 0.001). However, regarding PON1 Q192R, the R mutated allele frequency was found in 28.5% in RPL and in 33% in controls. The R allele did not show any risk for RPL (ORadj 0.81; 95%CI; p = 0.329).

Conclusion The present study suggests that there is an effect of genetic polymorphism on RPL and provides additional evidence that combines with the growing information about the ways in which certain PON1 genotypes can affect the development of the fetus in the uterus.

Resumo

Objetivo O objetivo deste estudo foi examinar a relação entre os polimorfismos PON1 e perda recorrente de gravidez PRG.

Métodos Em um estudo transversal, foram coletadas amostras de sangue de 100 mulheres. O DNA foi extraído e os genótipos PON1 foram determinados por amplificação por PCR.

Resultados Com relação ao PON1 L55M, a frequência do alelo mutado (M) foi encontrada em 70,5% no PRG e em 53,5% nos controles; o alelo M foi significativamente associado a um risco aumentado de PRG (odds radio ajustado [ORadj] =2,07; intervalo de confiança [IC] 95%; p < 0,001). No entanto, em relação ao PON1 Q192R, a frequência do alelo mutado R foi encontrada em 28,5% no PRG e em 33% nos controles. O alelo R não mostrou qualquer risco para PRG (ORadj 0,81; IC 95; p = 0,329).

Conclusão O presente estudo sugere que há um efeito do polimorfismo genético sobre PRG e fornece evidências adicionais que se combinam com as informações crescentes sobre as maneiras pelas quais certos genótipos PON1 podem afetar o desenvolvimento do feto no útero.

Keywords

recurrent pregnancy loss - paraoxonase 1 - organophosphate - pesticides - oxidative stress

Palavras-chave

perda de gravidez recorrente - paraoxonase 1 - organofosfato - pesticidas - estresse oxidativo

Contributions

Jaiswar S. P.: conceptualization, methodology, project administration, supervision. Priyadarshini A.: writing, review and editing. Singh A.: investigation, writing of the original draft, data curation, formal analysis. Ahmad M. K.: validation, doftware, resources. Deo S.: supervision. Sankhwar P.: data curation.




Publikationsverlauf

Eingereicht: 21. Dezember 2020

Angenommen: 03. September 2021

Artikel online veröffentlicht:
06. Dezember 2021

© 2021. Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

 

  • References

  • 1 Badawy SZ, Westpfal EM. Frequency of etiological factors and cost effectiveness of the work up for patients with history of recurrent pregnancy loss. Early Pregnancy 2000; 4 (04) 253-260
    PubMedGoogle Scholar
  • 2 Simpson JL, Carson S. Biological causes of fetal loss. In: Gray R, Leridon L, Spira F. editors. Biomedical and demographic determinants of reproduction. Oxford: Clarendon Press; 1993: 237-49
    Google Scholar
  • 3 Cramer DW, Wise LA. The epidemiology of recurrent pregnancy loss. Semin Reprod Med 2000; 18 (04) 331-339 DOI: 10.1055/s-2000-13722.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 4 Possamai FP, Fortunato JJ, Feier G, Agostinho FR, Quevedo J, Wilhelm FilhoD. et al. Oxidative stress after acute and sub-chronic malathion intoxication in Wistar rats. Environ Toxicol Pharmacol 2007; 23 (02) 198-204 DOI: 10.1016/j.etap.2006.09.003.
    CrossrefPubMedGoogle Scholar
  • 5 Abdollahi M, Ranjbar A, Shadnia S, Nikfar S, Rezaie A. Pesticides and oxidative stress: a review. Med Sci Monit 2004; 10 (06) RA141-RA147
    PubMedGoogle Scholar
  • 6 Hanke W, Jurewicz J. The risk of adverse reproductive and developmental disorders due to occupational pesticide exposure: an overview of current epidemiological evidence. Int J Occup Med Environ Health 2004; 17 (02) 223-243
    PubMedGoogle Scholar
  • 7 Martinelli N, Consoli L, Girelli D, Grison E, Corrocher R, Olivieri O. Paraoxonases: ancient substrate hunters and their evolving role in ischemic heart disease. Adv Clin Chem 2013; 59: 65-100 DOI: 10.1016/b978-0-12-405211-6.00003-6.
    CrossrefPubMedGoogle Scholar
  • 8 James RW. A long and winding road: defining the biological role and clinical importance of paraoxonases. Clin Chem Lab Med 2006; 44 (09) 1052-1059 DOI: 10.1515/CCLM.2006.207.
    CrossrefPubMedGoogle Scholar
  • 9 Chen D, Hu Y, Chen C, Yang F, Fang Z, Wang L. et al. Polymorphisms of the paraoxonase gene and risk of preterm delivery. Epidemiology 2004; 15 (04) 466-470 DOI: 10.1097/01.ede.0000129509.59912.b2.
    CrossrefPubMedGoogle Scholar
  • 10 Costa LG, Cole TB, Furlong CE. Polymorphisms of paraoxonase (PON1) and their significance in clinical toxicology of organophosphates. J Toxicol Clin Toxicol 2003; 41 (01) 37-45 DOI: 10.1081/clt-120018269.
    CrossrefPubMedGoogle Scholar
  • 11 Tsatsakis AM, Tutudaki M, Tzatzarakis MN, Dawson A, Mohamed F, Christaki M. et al. Is hair analysis for dialkyl phosphate metabolites a suitable biomarker for assessing past acute exposure to organophosphate pesticides?. Hum Exp Toxicol 2012; 31 (03) 266-273 DOI: 10.1177/0960327111403171.
    CrossrefPubMedGoogle Scholar
  • 12 Blanco-Muñoz J, Morales MM, Lacasaña M, Aguilar-Garduño C, Bassol S, Cebrián ME. Exposure to organophosphate pesticides and male hormone profile in floriculturist of the state of Morelos, Mexico. Hum Reprod 2010; 25 (07) 1787-1795 DOI: 10.1093/humrep/deq082.
    CrossrefPubMedGoogle Scholar
  • 13 Perera FP, Rauh V, Tsai WY, Kiney P, Camann D, Barr D. et al. Effects of transplacental exposure to environmental pollutants on birth outcomes in a multiethnic population. Environ Health Perspect 2003; 111 (02) 201-205 DOI: 10.1289/ehp.5742.
    CrossrefPubMedGoogle Scholar
  • 14 Berkowitz GS, Wetmur JG, Birman-Deych E, Obel J, Lapinski RH, Goodbold JH. et al. In utero pesticide exposure, maternal paraoxonase activity, and head circumference. Environ Health Perspect 2004; 112 (03) 388-391 DOI: 10.1289/ehp.6414.
    CrossrefPubMedGoogle Scholar
  • 15 Wolff MS, Engel S, Berkowitz G, Teitelbaum S, Siskind J, Barr DB. et al. Prenatal pesticide and PCB exposures and birth outcomes. Pediatr Res 2007; 61 (02) 243-250 DOI: 10.1203/pdr.0b013e31802d77f0.
    CrossrefPubMedGoogle Scholar
  • 16 Moreno-Banda G, Blanco-Muñoz J, Lacasaña M, Rothenberg SJ, Aguilar-Garduño C, Gamboa R. et al. Maternal exposure to floricultural work during pregnancy, PON1 Q192R polymorphisms and the risk of low birth weight. Sci Total Environ 2009; 407 (21) 5478-5485 DOI: 10.1016/j.scitotenv.2009.06.033.
    CrossrefPubMedGoogle Scholar
  • 17 Toy H, Camuzcuoglu H, Celik H, Erel O, Aksoy N. Assessment of serum paraoxonase and arylesterase activities in early pregnancy failure. Swiss Med Wkly 2009; 139 (5-6): 76-81
    PubMedGoogle Scholar
  • 18 Blanco-Muñoz J, Aguilar-Garduño C, Gamboa-Avila R, Rodríguez-Barranco M, Pérez-Méndez O, Huesca-Gómez C. et al. Association between PON1 genetic polymorphisms and miscarriage in Mexican women exposed to pesticides. Sci Total Environ 2013; 449: 302-308 DOI: 10.1016/j.scitotenv.2013.01.034.
    CrossrefPubMedGoogle Scholar
  • 19 Lawlor DA, Gaunt TR, Hinks LJ, Smith GD, Timpson N, Day INM. et al. The association of the PON1 Q192R polymorphism with complications and outcomes of pregnancy: findings from the British Women's Heart and Health cohort study. Paediatr Perinat Epidemiol 2006; 20 (03) 244-250 DOI: 10.1111/j.1365-3016.2006.00716.x.
    CrossrefPubMedGoogle Scholar
  • 20 Ryckman KK, Morken NH, White MJ, Velez DR, Menon R, Fortunato SJ. et al. Maternal and fetal genetic associations of PTGER3 and PON1 with preterm birth. PLoS One 2010; 5 (02) e9040 DOI: 10.1371/journal.pone.0009040.
    CrossrefPubMedGoogle Scholar
  • 21 Aviram M, Rosenblat M, Bisgaier CL, Newton RS, Primo-Parmo SL, La Du BN. Paraoxonase inhibits high-density lipoprotein oxidation and preserves its functions. A possible peroxidative role for paraoxonase. J Clin Invest 1998; 101 (08) 1581-1590 DOI: 10.1172/JCI1649.
    CrossrefPubMedGoogle Scholar
  • 22 Mackness MI, Arrol S, Abbott C, Durrington PN. Protection of low-density lipoprotein against oxidative modification by high-density lipoprotein associated paraoxonase. Atherosclerosis 1993; 104 (1-2): 129-135 DOI: 10.1016/0021-9150(93)90183-u.
    CrossrefPubMedGoogle Scholar
  • 23 Cao H, Girard-Globa A, Berthezene F, Moulin P. Paraoxonase protection of LDL against peroxidation is independent of its esterase activity towards paraoxon and is unaffected by the Q–>R genetic polymorphism. J Lipid Res 1999; 40 (01) 133-139
    CrossrefPubMedGoogle Scholar
  • 24 Bhattacharyya T, Nicholls SJ, Topol EJ, Zhang R, Yang X, Schmitt D. et al. Relationship of paraoxonase 1 (PON1) gene polymorphisms and functional activity with systemic oxidative stress and cardiovascular risk. JAMA 2008; 299 (11) 1265-1276 DOI: 10.1001/jama.299.11.1265.
    CrossrefPubMedGoogle Scholar
  • 25 Milatovic D, Gupta RC, Aschner M. Anticholinesterase toxicity and oxidative stress. ScientificWorldJournal 2006; 6: 295-310 DOI: 10.1100/tsw.2006.38.
    CrossrefPubMedGoogle Scholar
  • 26 Amer M, Metwalli M, Abu el-Magd Y. Skin diseases and enzymatic antioxidant activity among workers exposed to pesticides. East Mediterr Health J 2002; 8 (2-3): 363-373
    CrossrefPubMedGoogle Scholar
  • 27 Gultekin F, Ozturk M, Akdogan M. The effect of organophosphate insecticide chlorpyrifos-ethyl on lipid peroxidation and antioxidant enzymes (in vitro). Arch Toxicol 2000; 74 (09) 533-538 DOI: 10.1007/s002040000167.
    CrossrefPubMedGoogle Scholar
  • 28 Settimi L, Spinelli A, Lauria L, Miceli G, Pupp N, Angotzi G. et al. Spontaneous abortion and maternal work in greenhouses. Am J Ind Med 2008; 51 (04) 290-295 DOI: 10.1002/ajim.20556.
    CrossrefPubMedGoogle Scholar
  • 29 Arbuckle TE, Lin Z, Mery LS. An exploratory analysis of the effect of pesticide exposure on the risk of spontaneous abortion in an Ontario farm population. Environ Health Perspect 2001; 109 (08) 851-857 DOI: 10.1289/ehp.01109851.
    CrossrefPubMedGoogle Scholar
  • 30 Crisostomo L, Molina VV. Pregnancy outcomes among farming households of Nueva Ecija with conventional pesticide use versus integrated pest management. Int J Occup Environ Health 2002; 8 (03) 232-242 DOI: 10.1179/107735202800338812.
    CrossrefPubMedGoogle Scholar