[KSCI] Korea Science Citation Index Service

http://dx.doi.org/10.5808/GI.2008.6.2.077

Identification of Human LRG1 Polymorphisms and Their Genetic Association with Rheumatoid Arthritis

Jin, Eun-Heui (Genome Research Center for Immune Disorders, Wonkwang University School of Medicine)
Chae, Soo-Cheon (Department of Pathology, Wonkwang University School of Medicine)
Shim, Seung-Cheol (Division of Rheumatology, Department of Internal Medicine, Eulji University School of Medicine)
Kim, Hwan-Gyu (Division of Biological Sciences, Research Center of Bioactive Materials, Chonbuk National University)
Chung, Hun-Taeg (Genome Research Center for Immune Disorders, Wonkwang University School of Medicine)

Publication Information

Abstract

Human leucine-rich alpha-2-glycoprotein 1 (LRG1) was first identified as a trace protein in human serum. The primary sequence of LRG1 includes repeated leucine residues and putative membrane-binding domains. But, there is no published information on the genetic variation of this gene. In this study, LRG1 was identified as one of several upregulated genes in RA patients. We examined the expression levels of LRG1 between an RA patient and a healthy control by RT-PCR and validated that LRG1 was highly expressed in RA patients compared with controls. We identified the possible variation sites and single nucleotide polymorphisms (SNPs) in the human LRG1 gene by direct sequencing and analyzed the association of genotype and allele frequencies between RA patients and a control group without RA. We further investigated the relationship between these polymorphisms and the level of RF or anti-CCP in RA patients. We identified a total of three SNPs(g.-678A>G, g.-404C>T and g.1427T>C) and two variation sites (g.-1198delA and g.-893delA) in the LRG1 gene. Our results suggest that polymorphisms of the LRG1 gene are not associated with the susceptibility of RA in the Korean population.

Keywords

HRM; LRG1; polymorphism; rheumatoid arthritis;

Citations & Related Records

Reference

1	Li, X., Miyajima, M., Mineki, R., Taka, H., Murayama, K., and Arai, H. (2006). Analysis of potential diagnostic biomarkers in cerebrospinal fluid of idiopathic normal pressure hydrocephalus by proteomics. Acta. Neurochir. (Wien) 148, 859-864. DOI
2	Okano, T., Kondo, T., Kakisaka, T., Fujii, K., Yamada, M., Kato, H., Nishimura, T., Gemma, A., Kudoh, S., and Hirohashi, S. (2006). Plasma proteomics of lung cancer by a linkage of mlti-dimensional liquid chromatography and two-dimensional difference gel electrophoresis. Proteomics. 6, 3938-3948. DOI ScienceOn
3	Schellekens, G.A., Visser, H., de Jong, B.A., van den Hoogen, F.H., Hazes, J.M., Breedveld, F.C., and van Venrooij, W.J. (2000). The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum. 43, 155-163. DOI ScienceOn
4	Schena, M., Shalon, D., Davis, R.W., and Brown, P.O. (1995). Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 270, 467-470. DOI ScienceOn
5	Suzuki, A., Yamada, R., Chang, X., Tokuhiro, S., Sawada, T., Suzuki, M., Nagasaki, M., Nakayama-Hamada, M., Kawaida, R., Ono, M., Ohtsuki, M., Furukawa, H., Yoshino, S., Yukioka, M., Tohma, S., Matsubara, T., Wakitani, S., Teshima, R., Nishioka, Y., Sekine, A., Iida, A., Takahashi, A., Tsunoda, T., Nakamura, Y., and Yamamoto, K. (2003). Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis. Nat. Genet. 34, 395-402. DOI ScienceOn
6	Tokuhiro, S., Yamada, R., Chang, X., Suzuki, A., Kochi, Y., Sawada, T., Suzuki, M., Nagasaki, M., Ohtsuki, M., Ono, M., Furukawa, H., Nagashima, M., Yoshino, S., Mabuchi, A., Sekine, A., Saito, S., Takahashi, A., Tsunoda, T., Nakamura, Y., and Yamamoto, K. (2003). An intronic SNP in a RUNX1 binding site of SLC22A4, encoding an organic cation transporter, is associated with rheumatoid arthritis. Nat. Genet. 35, 341-348. DOI ScienceOn
7	Newmeyer, D.D., and Ferguson-Miller, S. (2003). Mitochondria: releasing power for life and unleashing the machineries of death. Cell 112, 481-490. DOI ScienceOn
8	Tighe, H., and Carson, D.A. (2001). Rheumatoid factor. In Kelley's Textbook of Rheumatology, Ruddy, S., Harris, E. D., Sledge, C., eds. (Philadelphia: W.B. Saunders Company), pp.151-161.
9	Takahashi, N., Takahashi, Y., and Putnam, F.W. (1985). Periodicity of leucine and tandem repetition of a 24-amino acid segment in the primary structure of leucine-rich ${\alpha}2-glycoprotein$ of human serum. Proc. Natl. Acad. Sci. USA 82, 1906-1910 DOI ScienceOn
10	Shalon, D., Smith, S., and Brown, P.O. (1996). A DNA microarray system for analyzing complex DNA samples using two-color fluorescent probe hybridization. Genome Res. 6, 639-645. DOI ScienceOn
11	Waaler, E. (1940). On the occurrence of a factor in human serum activating the specific agglutination of sheep blood corpuscles. Acta. Pathol. Microbiol. Scand. 17, 172. DOI
12	Batliwalla, F.M., Baechler, E.C., Xiao, X., Li, W., Balasubramanian, S., Khalili, H., Damle, A., Ortmann, W.A., Perrone, A., Kantor, A.B., Gulko, P.S., Kern, M., Furie, R., Behrens, T.W., and Gregersen, P.K. (2005). Peripheral blood gene expression profiling in rheumatoid arthritis. Genes. Immunol. 6, 388-397. DOI ScienceOn
13	Blass, S., Union, A., Raymackers, J., Schumann, F., Ungethum, U., Muller-Steinbach, S., De Keyser, F., Engel, J.M., and Burmester, G.R. (2001). The stress protein BiP is overexpressed and is a major B and T cell target in rheumatoid arthritis. Arthritis Rheum. 44, 761-771. DOI ScienceOn
14	Gregerin, P.K. (1999). Genetics of rheumatoid arthritis : confronting complexity. Arthritis Res. 1, 37-44. DOI ScienceOn
15	Kakisaka, T., Kondo, T., Okano, T., Fujii, K., Honda, K., Endo, M., Tsuchida, A., Aoki, T., Itoi, T., Moriyasu, F., Yamada, T., Kato, H., Nishimura, T., Todo, S., and Hirohashi, S. (2007). Plasma proteomics of pancreatic cancer patients by multi-dimensional liquid chromatography and two-dimensional difference gel electrophoresis (2D-DIGE) : Up-regulation of leucine-rich alpha-2-glycoprotein in pancreatic cancer. J. Chroma. B. 852, 257-267. DOI ScienceOn
16	Blass, S., Engel, J.M., and Burmester, G.R. (1999). The immunologic homunculus in rheumatoid arthritis. Arthritis Rheum. 42, 2499-2506. DOI ScienceOn
17	Kawakami, T., Hoshida, Y., Kanai, F., Tanaka, Y., Tateishi, K., Ikenoue, T., Obi, S., Sato, S., Teratani, T., Shiina, S., Kawabe, T., Suzuki, T., Hatano, N., Taniguchi, H., and Omata, M. (2005). Proteomic analysis of sera from hepatocellular carcinoma patients after radiofrequency ablation treatment. Proteomics 5, 4287-4295. DOI ScienceOn
18	Kobe, B., and Deisenhofer, J. (1994). The leucine-rich repeat : a versatile binding motif. TIBS. 19, 415-421. DOI ScienceOn
19	Haupt, H., and Baudner, S. (1977). Isolation and characterization of an unknown, leucine-rich 3.1-S-alpha2-glycoprotein from human serum. Hoppe Seylers Z. Phisiol. Chem. (article in German). 358, 639-646. DOI
20	Heller, R.A., Schena, M., Chai, A., Shalon, D., Bedilion, T., Gilmore, J., Woolley, D.E., and Davis, R.W. (1997). Discovery and analysis of inflammatory disease-related genes using cDNA microarrays. Proc. Natl. Acad. Sci. USA. 94, 2150-2155. DOI ScienceOn
21	Pullerits, R., Bokarewa, M., Jonsson, I.M., Verdrengh, M., and Tarkowski, A. (2005). Extracellular cytochrome c, a mitochondrial apoptosis-related protein, induces arthritis. Rheumatology 44, 32-39. DOI ScienceOn
22	Li, X., Miyajima, M., Jiang, C., and Arai, H. (2007). Expression of $TGF-{\beta}s$ and $TGF-{\beta}$ type II receptor in cerebrospinal fluid of patients with idiopathic normal pressure hydrocephalus. Neuro. Letters 413, 141-144. DOI ScienceOn
23	Baechler, E.C., Batliwalla, F.M., Karypis, G., Gaffney, P.M., Ortmann, W.A., Espe, K.J., Shark, K.B., Grande, W.J., Hughes, K.M., Kapur, V., Gregersen, P.K., and Behrens, T.W. (2003). Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc. Natl. Acad. Sci. USA. 100, 2610-2615 DOI ScienceOn
24	Shukaili, A., and Jabri, A. (2006). Rheumatoid arthritis, cytokines and hypoxia. What is the link? Saudi Med. J. 27, 1642-1649.
25	Bomprezzi, R., Ringner, M., Kim, S., Bittner, M.L., Khan, J., Chen, Y., Elkahloun, A., Yu, A., Bielekova, B., Meltzer, P.S., Martin, R., McFarland, H.F., and Trent, J.M. (2003). Gene expression profile in multiple sclerosis patients and healthy controls: identifying pathways relevant to disease. Hum. Mol. Genet. 12, 2191-2199. DOI ScienceOn
26	Buchanan, S.G., and Gay, N.J. (1996). Structural and functional diversity in the leucine-rich repeat family of proteins. Prog. Bioohys. Mol. Biol. 65, 1-44.