Original Article
  

Association of CD46 IVS1-1724 C>G Single Nucleotide Polymorphism in Iranian Women with Unexplained Recurrent Spontaneous Abortion (URSA)

Abstract

There are several known and unknown factors for unexplained recurrent spontaneous abortion (URSA). Among them, complement regulatory protein CD46 plays a pivotal role in preventing uncontrolled activation of complement and successful continuation of pregnancy. We aimed in this study to investigate the possible association of CD46 IVS1-1724 C>G polymorphism with RSA in Iranian women. 141 women with RSA and 153 women with normal pregnancy were enrolled in this study. RSA was confirmed as the history of having at least three consecutive abortions without any known immunologic, pathologic and genetic reason. Genomic DNA was extracted and RFLP-PCR was done using a specific primer pair and HindIII restriction enzyme. Statistical analysis was done for determining the genotype and allele frequency, and also for odds ratio (OR). Statistical analysis showed no significant difference in genotype frequency between two RSA and normal groups. However G allele was significantly more frequent in fertile women and represented as a protective allele (p=0.04, OR=0.8, CI 95%). In contrary to similar studies in other two ethnic populations, our study showed no genotype differences in CD46 IVS1-1724 C>G Single nucleotide polymorphis (SNP) between RSA and fertile women. On the other hand, G allele was revealed as a protective allele for RSA. CD46 polymorphisms may predict the outcome of pregnancy; however, more studies in different ethnic groups are required.

 

1. Pandey MK, Rani R, Agrawal S. An update in recurrent spontaneous abortion. Arch Gynecol Obstet 2005, 272(2):95-108.
2. Branch DW, Gibson M, Silver RM. Clinical practice. Recurrent miscarriage. N Engl J Med 2010, 363(18):1740-7.
3. Tincani A, Cavazzana I, Ziglioli T, Lojacono A, De Angelis V, Meroni P. Complement activation and pregnancy failure. Clin Rev Allergy Immunol 2010, 39(3):153-9.
4. Liszewski MK, Post TW, Atkinson JP. Membrane cofactor protein (MCP or CD46): newest member of the regulators of complement activation gene cluster. Annu Rev Immunol 1991, 9:431-55.
5. Liszewski MK, Kemper C, Price JD, Atkinson JP. Emerging roles and new functions of CD46. Springer Semin Immunopathol 2005, 27(3):345-58.
6. Hourcade D, Liszewski MK, Krych-Goldberg M, Atkinson JP. Functional domains, structural variations and pathogen interactions of MCP, DAF and CR1. Immunopharmacology 2000, 49(1-2):103-16.
7. Seya T, Hirano A, Matsumoto M, Nomura M, Ueda S. Human membrane cofactor protein (MCP, CD46): multiple isoforms and functions. Int J Biochem Cell Biol 1999, 31(11):1255-60.
8. Salmon JE, Heuser C, Triebwasser M, Liszewski MK, Kavanagh D, Roumenina L, et al. Mutations in complement regulatory proteins predispose to preeclampsia: a genetic analysis of the PROMISSE cohort. PLoS Med 2011, 8(3):e1001013.
9. Lokki AI, Aalto-Viljakainen T, Meri S, Laivuori H, Finnpec. Genetic analysis of membrane cofactor protein (CD46) of the complement system in women with and without preeclamptic pregnancies. PloS one 2015, 10(2):e0117840.
10. Richards A, Kathryn Liszewski M, Kavanagh D, Fang CJ, Moulton E, Fremeaux-Bacchi V, et al. Implications of the initial mutations in membrane cofactor protein (MCP; CD46) leading to atypical hemolytic uremic syndrome. Mol Immunol 2007, 44(1-3):111-22.
11. Richards A, Kemp EJ, Liszewski MK, Goodship JA, Lampe AK, Decorte R, et al: Mutations in human complement regulator, membrane cofactor protein (CD46), predispose to development of familial hemolytic uremic syndrome. Proc Natl Acad Sci U S A 2003, 100(22):12966-71.
12. Risk JM, Flanagan BF, Johnson PM. Polymorphism of the human CD46 gene in normal individuals and in recurrent spontaneous abortion. Hum Immunol 1991, 30(3):162-7.
13. Wang ZC, Hill JA, Yunis EJ, Xiao L, Anderson DJ. Maternal CD46H*2 and IL1B-511*1 homozygosity in T helper 1-type immunity to trophoblast antigens in recurrent pregnancy loss. Hum Reprod 2006, 21(3):818-22.
14. Bora NS, Post TW, Atkinson JP. Membrane cofactor protein of the complement system. A HindIII restriction fragment length polymorphism that correlates with the expression polymorphism. J Immunol 1991, 146(8):2821-5.

15. Zutshi N, Gandhi M, Kaul P. CD46 polymorphism: a probable risk factor for recurrent spontaneous abortion in a northern Indian population. Natl Med J India 2010, 23(2):85-7.
16. Miller SA, Dykes DD, Polesky HF: A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic acids research 1988, 16(3):1215.
17. Karp CL, Wysocka M, Wahl LM, Ahearn JM, Cuomo PJ, Sherry B, et al. Mechanism of suppression of cell-mediated immunity by measles virus. Science 1996, 273(5272):228-31.
18. Dorig RE, Marcil A, Chopra A, Richardson CD. The human CD46 molecule is a receptor for measles virus (Edmonston strain). Cell 1993, 75(2):295-305

Files
IssueVol 15, No 4 (2016) QRcode
SectionOriginal Article(s)
Keywords
Abortion CD46 PCR-RFLP Recurrent spontaneous abortion Single nucleotide polymorphis
Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
1.
Abdi-Shayan S, Monfaredan A, Moradi Z, Rajaii Oskoui M, Kazemi T. Association of CD46 IVS1-1724 C>G Single Nucleotide Polymorphism in Iranian Women with Unexplained Recurrent Spontaneous Abortion (URSA). Iran J Allergy Asthma Immunol. 2016;15(4):303-308.