Korean J Ophthalmol.  2007 Mar;21(1):33-38. 10.3341/kjo.2007.21.1.33.

Investigation of the Association between Normal-tension Glaucoma and Single Nucleotide Polymorphisms in Natriuretic Peptide Gene

• Jeoung JW
• Kim DM
• Ko HS
• Park SS
• Kim JY
• Kim SY
• Yoo TW

• KMID: 1105028
• DOI: http://doi.org/10.3341/kjo.2007.21.1.33

Abstract

PURPOSE: The expression of natriuretic peptides in the neural bundles of the anterior portion of the optic nerves and their functions in regulating vessel tone and blood flow may suggest a possible role in the pathogenesis of glaucoma. The purpose of this study was to investigate the association between normal-tension glaucoma and the genetic variations of atrial natriuretic peptide (Nppa) and natriuretic peptide receptor A (Npr1) gene. METHODS: Sixty-seven Korean normal-tension glaucoma (NTG) patients and 100 healthy subjects (as normal controls) were enrolled. DNA from peripheral blood leukocytes was extracted, and the genotypes of five polymorphisms (c.94G>A, c.454T>C, IVS1+16C>T, IVS2+701G>A, and c.-764C>G) in the Nppa gene and one polymorphism (c.1023G>C) in the Npr1 gene were determined using the restriction fragment length polymorphism and the SNaPshot methods. The genotype and allele frequencies of these polymorphisms in patients with NTG and normal controls were compared using the Fisher's exact test and the chi-square test. RESULTS: In both groups, the genotype distributions were in accordance with the Hardy-Weinberg equilibrium. There was no significant difference in the frequency of the Nppa and Npr1 alleles or genotypes in the normal-tension glaucoma group as compared to the control group. CONCLUSIONS: Nppa and Npr1 gene polymorphisms are not associated with normal-tension glaucoma, suggesting that this gene does not have an important role in the pathogenesis of optic neuropathy in this disease.

Keyword

Atrial natriuretic peptide; Natriuretic peptide receptor A; Normal-tension glaucoma; Single nucleotide polymorphism

MeSH Terms

Receptors, Atrial Natriuretic Factor/*genetics
*Polymorphism, Single Nucleotide
Middle Aged
Male
*Intraocular Pressure
Humans
Guanylate Cyclase/*genetics
Glaucoma/genetics/*physiopathology
Genotype
Gene Frequency
Female
Atrial Natriuretic Factor/*genetics
Adult

Figure

• 

  Fig. 1 Genomic structures. (A) Nppa gene; (B) Npr1 gene (provided in the public domain by the National Center for Biotechnology Information, Bethesda, MD, U. S. A.; available at http://www.ncbi.nlm.nih.gov).

Reference

1. Goldberg I, Hollows FC, Kass MA, Becker B. Systemic factors in patients with low-tension glaucoma. Br J Ophthalmol. 1981. 65:56–62.

2. de Bold AJ. Atrial natriuretic factor: a hormone produced by the heart. Science. 1985. 230:767–770.

3. Sudoh T, Kangawa K, Minamino N, Matsuo H. A new natriuretic peptide in porcine brain. Nature. 1988. 332:78–81.

4. Sudoh T, Minamino N, Kangawa K, Matsuo H. C-type natriuretic peptide (CNP): a new member of natriuretic peptide family identified in porcine brain. Biochem Biophys Res Commun. 1990. 168:863–870.

5. de Bold AJ, Flynn TG. Cardionatrin I-a novel heart peptide with potent diuretic and natriuretic properties. Life Sci. 1983. 33:297–302.

6. Suga SI, Nakao K, Hosada K, et al. Receptor selectivity of natriuretic peptide family, atrial natriuretic peptide, brain natriuretic peptide, and C-type natriuretic peptide. Endocrinology. 1992. 130:229–239.

7. Levin ER, Gardner DG, Samson WK. Natriuretic Peptides. N Engl J Med. 1998. 339:321–328.

8. Schulz S, Singh S, Bellet RA, et al. The primary structure of a plasma membrane guanylate cyclase demonstrates diversity within this new receptor family. Cell. 1989. 58:1155–1162.

9. Itoh H, Pratt RE, Ohno M, Dzau VJ. Atrial natriuretic polypeptide as a novel antigrowth factor of endothelial cells. Hypertension. 1992. 19:758–761.

10. Levin ER, Frank HJ. Natriuretic peptides inhibit rat astroglial proliferation: mediation by C receptor. Am J Physiol. 1991. 261:R453–R457.

11. Pedram A, Razandi M, Levin ER. Natriuretic peptides suppress vascular endothelial cell growth factor signaling to angiogenesis. Endocrinology. 2001. 142:1578–1586.

12. Rollin R, Mediero A, Roldan-Pallares M, et al. Natriuretic peptide system in the human retina. Mol Vis. 2004. 10:15–22.

13. Povey S, Lovering R, Bruford E, et al. The HUGO Gene Nomenclature Committee (HGNC). Hum Genet. 2001. 109:678–680.

14. Agresti A. A survey of exact inference for contingency tables. Stat Sci. 1992. 7:131–177.

15. Nicolela MT, Ferrier SN, Morrison CA, et al. Effects of cold-induced vasospasm in glaucoma: the role of endothelin-1. Invest Ophthalmol Vis Sci. 2003. 44:2565–2572.

16. Buckley C, Hadoke PW, Henry E, O'Brien C. Systemic vascular endothelial cell dysfunction in normal pressure glaucoma. Br J Ophthalmol. 2002. 86:227–232.

17. Gass A, Flammer J, Linder L, et al. Inverse correlation between endothelin-1-induced peripheral microvascular vasoconstriction and blood pressure in glaucoma patients. Graefes Arch Clin Exp Ophthalmol. 1997. 235:634–638.

18. Drance SM, Sweeney VP, Morgan RW, Feldman F. Studies of factors involved in the production of low tension glaucoma. Arch Ophthalmol. 1973. 89:457–465.

19. Nilsson SF. Neuropeptide Y (NPY): a vasoconstrictor in the eye, brain and other tissues in the rabbit. Acta Physiol Scand. 1991. 141:455–467.

20. Swedlund AP, Rosenzweig SA. Characterization of vasoactive intestinal peptide receptors in retina. Exp Eye Res. 1990. 51:317–323.

21. Wiggins AK, Shen PJ, Gundlach AL. Atrial natriuretic peptide expression is increased in rat cerebral cortex following spreading depression: possible contribution to sd-induced neuroprotection. Neuroscience. 2003. 118:715–726.

22. Gruchala M, Ciecwierz D, Wasag B, et al. Association of the ScaI atrial natriuretic peptide gene polymorphism with nonfatal myocardial infarction and extent of coronary artery disease. Am Heart J. 2003. 145:125–131.

23. Rutledge D, Sun Y, Ross E. Polymorphisms within the atrial natriuretic peptide gene in essential hypertension. J Hypertens. 1995. 13:953–955.

24. Barley J, Carter N, Cruickshank J, et al. Renin and atrial natriuretic peptide restriction fragment length polymorphisms: association with ethnicity and blood pressure. J Hypertens. 1991. 9:993–996.

25. Schorr U, Beige J, Ringel J, et al. HpaII polymorphism of the atrial natriuretic peptide gene and the blood pressure response to salt intake in normotensive men. J Hypertens. 1997. 15:715–718.

26. Chiang F, Tseng C, Hsu K, et al. Atrial natriuretic peptide gene polymorphism is not associated with essential hypertension: evidence of association with ethnic origin. J Hum Hypertens. 1996. 10:334.

27. Simon J, Krege J, Oliver P, et al. Genetic decreases in atrial natriuretic peptide and salt-sensitive hypertension. Science. 1995. 267:679–681.

28. Kato N, Sugiyama T, Morita H, et al. Genetic analysis of the atrial natriuretic peptide gene in essential hypertension. Clin Sci. 2000. 98:251–258.

29. Nannipieri M, Manganiello M, Pezzatini A, et al. Polymorphisms in the hANP (human atrial natriuretic peptide) gene, albuminuria, and hypertension. Hypertension. 2001. 37:1416–1422.

30. Ramasawmy R, Kotea N, Lu CY, et al. Investigation of the polymorphic ScaI site by a PCR-based assay at the human atrial natriuretic peptides (hANP) gene locus. Hum Genet. 1992. 90:323–324.

31. Oh JH. Study on the polymorphisms of the genes associated with renin-angiotensin, kallikrein-kinin and natriuretic peptide systems in Koreans. Master's thesis of Seoul National University. 1999. 1–46.

32. Rubattu S, Stanzione R, Di Angelantonio E, et al. Atrial natriuretic peptide gene polymorphisms and risk of ischemic stroke in humans. Stroke. 2004. 35:814–818.

33. Kato N, Sugiyama T, Morita H, et al. Genetic analysis of the atrial natriuretic peptide gene in essential hypertension. Clin Sci. 2000. 98:251–258.

34. Nakayama T, Soma M, Mizutani Y, et al. A novel missense mutation of exon 3 in the type A human natriuretic peptide receptor gene: possible association with essential hypertension. Hypertens Res. 2002. 25:395–401.

35. Nakayama T, Soma M, Saito S, et al. Missense mutation of exon 3 in the type A human natriuretic peptide receptor gene is associated with myocardial infarction. Med Sci Monit. 2003. 9:CR505–CR510.

36. Tunny TJ, Richardson KA, Clark CV, Gordon RD. The atrial natriuretic peptide gene in patients with familial primary open-angle glaucoma. Biochem Biophys Res Commun. 1996. 223:221–225.