ENDOTHELIAL NITRIC OXIDE SYNTHASE (ENOS) GENE POLYMORPHISM IS ASSOCIATED WITH AGE ONSET OF MENARCHE IN SICKLE CELL DISEASE FEMALES OF INDIA

Main Article Content

Sudhansu Sekhar Nishank

Keywords

Key words, eNOS gene, sickle cell disease, menarche, haplotype, nitric oxide

Abstract

ABSTRACT

 

Background and Objective :  Females with sickle cell disease (SCD) often show late onset of menarche. In transgenic sickle cell mouse, deficiency of gene encoding endothelial nitric oxide synthase (eNOS) has been reported to be associated with late onset of menarche. Thus to explore the possible association of eNOS gene polymorphism with age of onset of menarche in SCD females, 3 important eNOS gene polymorphism- eNOS 4a/b, eNOS 894G>T and eNOS-786 T>C  and  plasma nitrite levels were tested among three groups of females- SCD late menarche, SCD early menarche and control females.

Methods : PCR-RFLP method for genotyping eNOS gene polymorphisms and quantification of plasma nitrite level by ELISA based commercial kits were used

Results: SCD late menarche females showed significantly higher prevalence and higher association of heterozygous genotypes, higher frequency of mutant alleles ‘4a’, ‘T’ and ‘C’ as compared to that of control group and SCD early menarche group. The frequency of haplotype  ‘4a-G-C’ and haplotype’ 4b-G-C’ (alleles in order of  eNOS 4a/b, eNOS 894G>T and eNOS-786 T>C respectively) were found to be significantly high in SCD late menarche compared to combined groups of SCD early menarche and controls. SCD late menarche group had significantly low level of plasma nitrite concentration for all 3 eNOS gene polymorphisms as compared to controls and SCD early menarche females.

Conclusion: eNOS gene polymorphism may influence age of onset of menarche in SCD females.

 

Key words : eNOS gene, sickle cell disease, menarche, haplotype, nitric oxide

 

Downloads

Download data is not yet available.


Abstract 1081
PDF Downloads 542
HTML Downloads 2308
Table Downloads 0

References

1.Maul H., Longo M., Saade GR, Garfield RE. Nitric Oxide and its role during pregnancy: from
ovulation to delivery. Curr Phar Des. 2003; 9(5): 359-80

2.Faletti A, Pérez Martínez S, Perotti C, de Gimeno MA. Activity of ovarian nitric oxide
synthase (NOs) during ovulatory process in the rat: relationship with prostaglandins (PGs)
production. Nitric Oxide.1999; 3(4):340-7

3. Chwalisz K, Garfield RE. Role of nitric oxide in implantation and menstruation. Hum Reprod.
2000; Aug:15 Suppl 3: 96-111

4.Telfer JF, Irvine GA, Kohnen G, Campbell S and Cameroon IT. Expression of endothelial and
inducible nitric oxide synthase in non-pregnant and decidualized human endometrium.
Molecular Human Reproduction 1997; 3(1): 69-75

5.Cameron IT and Campbell S. Nitric oxide in endometrium. Human Reproduction Update.
1998; 4(5), 565- 569

6.Wang X Li, Wang J. Endothelial nitric oxide synthase gene sequence variations and vascular
disease. Molecular Genetics and Metabolism 2000; 70: 241-251

7.Tempfer C, Moreno RM, O’ Brien WE, Gregg AR. Genetic contributions of the endothelial
nitric oxide synthase gene to ovulation and menopause in a mouse model. Fertil Steril. 2000;
73:1025 – 31

8. Worda C, Walch K, Sator M, et al. The influence of Nos3 polymorphisms on age at menarche
and natural menopause, Maturitas 2004; 49: 157-162

9.Serjeant GR, Singhal A, Hambleton IR. Sickle cell disease and age at menarche in Jamaican
girls: observations from a cohort study. Arch Dis Child 2001; 85: 375-378

10. Balgir RS. Age at menarche and first conception in sickle cell hemoglobinopathy .Indian
Pediatrics 1994; 31: 827-832

11. Bagga A., Kulkarni S. Age at menarche and secular trend in Maharashtrian (Indian) girls.
Acta Biologica Szegediensis. 2000; 44:53-57

12.Akhtar MS, Biswas A, Ranjan R, Sharma A, Kumar S, Saxena R. The nitric oxide synthase 3
gene polymorphisms and their association with deep vein thrombosis in Asian Indian patients.
Clinica Chimica Acta 2010; 411: 649-652

13. Tang Z, Junyao Li , Jianhong MM, Jianhong Yang MM. Relationship of endothelial nitric
oxide synthase gene polymorphism with blood pressure, lipid profile and blood glucose
level.Front. Med. China. 2008; 2(2): 178-181

14 Sinici I, Guven EO, Serefoglu E, Hayran M. T-786C polymorphism in promoter of eNOS
gene as genetic risk factor in patients with erectile dysfunction in Turkish population.
J.Urology. Jun26.doi: 10.1016/j.urology.2009; 06.063


15. Tsukuda T, Yokoyama K, Arai T, takemoto F, Hara S, Yamada A. et al. Evidence of
association of the eNOS gene polymorphism with plasma NO metabolite levels in humans.
Biochem Biophy Res Commun 1998; 245:190-193

16. Fatini C, Sofi F, Gensini F, et al. Influence of eNOS gene polymorphisms on carotid
Atherosclerosis. Eur J Vasc Endovasc Surg 2004; 27: 540-544

17. Barbara V, Jin RC, Loscalzo J. Nitric oxide insufficiency and atherothrombosis. Histochem
Cell Biol. 2004; 122: 353-367

18. de Marco KC, Antunes LMG, Tanus-Santos JE, Barbosa Jr. F. Intron 4 polymorphism of the
endothelial nitric oxide synthase (eNOS) gene associated with decreased NO production in
mercury exposed population. Science of the Total Environment
doi:10.1016/j.scitotenv.2011.11.010

19. Rosselli M, Imthurm B, Macas E, Eller PJ and Dubey RK. Circulating nitrite/nitrate levels
increase with follicular development : indirect evidence foe estradiol mediated NO release.
Biochemical and Biophysical Research Communications.1994; 202: 1543-1552

20. Tao M, Kodama H, Kagabu S, et al. Possible contribution of follicular interleukin-1? to nitric
oxide generation in human pre-ovulatory follicles. Human reproduction. 1997; 12(10): 2220-
2225


21. Anteby EY, Hurwitz A, Korach O, et al. Human follicular ntric oxide pathway: relationship
to follicular size, oestradiol concentrations and ovarian blood flow. Human Reproduction
1996; 11: 1947-1951

22. Kharitonov SA, Logan-Sinclair RB, Musset CM, Shinebourne EA. Peak expiratory nitric
oxide differences in men and women: relation to the menstrual cycle. Br. Heart J 1994; 72:
243- 245

23. Tamanini C, Basin G, Grasselli F and Tirelli M. Nitric oxide and the ovary. Journal of
Animal Sciences, 2003; 81: E1- E7

24. Van Voorhis BJ, Moore K, Strijbos PJ, et al. Expression and localization of indicible and
endothelial nitric oxide synthase in the rat ovary. effects of gonadotropin stimulation in
vivo. J.of Clinical Investigation. 1995; 96: 2719- 2725
25. Jablonka –Shariff and Olson LM. . Hormonal regulation of nitric oxide synthases and their
cell specific expression during follicular development in the rat ovary. Endocrinology. 1997;
138:460-468

26. Sandrim VC, de Syllos RW, Lisboa HRK, Tres GS, Tanus-Santos JE. Influence of eNOS
haplotypes on the plasma nitric oxide products concentrations in hypertensive and type 2
diabetes mellitus patients. Nitric Oxide 2007; 16: 348-355


27. Metzger IF, Sertorio JTC, Tanus-Santos JE. Modulation of nitric oxide formation by
endothelial nitric oxide synthase gene haplotypes. Free radical Biology and Medicine. 2007;
43: 987-992

28. Holla LI, Jurajda M, Pohunek P, Znojil V. Haplotype analysis of the endothelial nitric
oxide synthase gene in asthma. Human Immunology. 2008; 69:306-313

29. He C, Kraft P, Chasman DI, Buring JE, Chen C, Hankinson SE, Paré G. et al. A large scale
candidate gene association study of age at menarche and age at natural menopause Hum
Genet. 2010 Nov;128(5):515-27. doi:10.1007/s00439-010-0878-4. Epub 2010 Aug 24.

30. Huber A., Grimm C., Jirecek S., Heim K., Zeillinger R., Husslein P. et al. Polymorphisms of
the NOS3 gene and unexplained late intrauterine fetal death. Eur. j. of Obst. and Gynecol.and
Repr. Biol. 2005; 122: 151-155


31.Yoshimura T., Yoshimura M., Tabata A., Yasue H., Okamura H., . The missense Glu298Asp
variant of the endothelial nitric oxide synthase gene is strongly associated with placental
abruption. Hum Genet. 2001; 108:181-183

32. Balgir RS. Infant mortality and reproductive wastage associated with different genotypes of
haemoglobinopathies in Orissa, India. Ann Hum Biol. 2007 Jan-Feb;34(1):16-25.

33. Chakravarty EF, Khanna D, Chung L. Pregnancy outcomes in systemic sclerosis, primary
pulmonary hypertension and sickle cell disease Obstet Gynecol. 2008 Apr;111(4):927-34.
doi: 10.1097/01.AOG.0000308710.86880.a6.


34. Al Kahtani MA, AlQahtani M, Alshebaily MM, Abd Elzaher M, Moawad A, Aljohani N.
Morbidity and pregnancy outcomes associated with sickle cell anemia among Saudi women.
Int J Gynaecol Obstet. 2012 Dec;119(3):224-6. doi: 10.1016/j.ijgo.2012.07.008.

35. Wilson NO, Ceesay FK, Hibbert JM, Driss A, Obed SA, Adjei AA. et al.Pregnancy
outcomes among patients with sickle cell disease at Korle-Bu Teaching Hospital, Accra
Ghana: retrospective cohort study. Am J Trop Med Hyg. 2012 Jun;86(6):936-42. doi:
10.4269/ajtmh.2012.11-0625.