TY - JOUR
T1 - Differential expression of alternative splice variants of CTLA4 in Kuwaiti autoimmune disease patients
AU - AlFadhli, Suad
AU - Nizam, Rasheeba
PY - 2014/1/25
Y1 - 2014/1/25
N2 - Cytotoxic T lymphocyte associated antigen4 (CTLA4) is a candidate susceptibility gene for the study of autoimmune diseases. The present study sought to explore the expression profile of the CTLA4 gene in autoimmune patients, such as rheumatoid arthritis (RA), systemic lupus erythematous (SLE) and Hashimoto's thyroiditis (HT), compared to healthy controls (HCs). A total of 88 (22 RA, 22 SLE 22 HT, 22 HCs) age-, gender- and ethnicity-matched individuals were recruited. The hypersensitive capillary electrophoresis method was employed to detect the CTLA4 splice variants. PCRs of the patient's cDNA using CTLA4-specific primers followed by cloning and sequencing were used to distinguish the various splice variants. The biochemical properties of all known CTLA4 variants were analysed using the ExPASy and ESEfinder programmes. Six alternatively spliced variants of the CTLA4 gene were detected in this study. These included mCTLA4-672, sCTLA4-562, N-CTLA4-292, L-CTLA4-277, ssCTLA4-214 and K-CTLA4-142. bp. K-CTLA4-142. bp and N-CTLA4-292. bp represented two novel splice variants of the CTLA4 gene. A reduction in the frequency of mCTLA4-672. bp and sCTLA4-562. bp was observed in SLE and RA patients compared to healthy controls. The shortest splice variant, K-CTLA4-142. bp, was predominantly detected in all of the tested cohorts, while the decreased expression of the N-CTLA4-292. bp variant was observed in the autoimmune subjects. The exonic splice enhancer motifs of the SRp40 protein were found exactly at the splice junction of wCTLA4 (-ACAGAGC-, 2.7) and K-CTLA4 (-TGAAAAG-, 3.37), and that of the SRp55 protein was found at the splice junction of L-CTLA4 (-TGTGTG-, 2.82). Our study highlights the discrepancies in the expression spectrum of the CTLA4 gene in autoimmune patients and healthy subjects. The abnormal expression pattern of the CTLA4 gene in autoimmune patients suggests that in addition to allelic variation, the expression pattern of CTLA4 could contribute to autoimmunity.
AB - Cytotoxic T lymphocyte associated antigen4 (CTLA4) is a candidate susceptibility gene for the study of autoimmune diseases. The present study sought to explore the expression profile of the CTLA4 gene in autoimmune patients, such as rheumatoid arthritis (RA), systemic lupus erythematous (SLE) and Hashimoto's thyroiditis (HT), compared to healthy controls (HCs). A total of 88 (22 RA, 22 SLE 22 HT, 22 HCs) age-, gender- and ethnicity-matched individuals were recruited. The hypersensitive capillary electrophoresis method was employed to detect the CTLA4 splice variants. PCRs of the patient's cDNA using CTLA4-specific primers followed by cloning and sequencing were used to distinguish the various splice variants. The biochemical properties of all known CTLA4 variants were analysed using the ExPASy and ESEfinder programmes. Six alternatively spliced variants of the CTLA4 gene were detected in this study. These included mCTLA4-672, sCTLA4-562, N-CTLA4-292, L-CTLA4-277, ssCTLA4-214 and K-CTLA4-142. bp. K-CTLA4-142. bp and N-CTLA4-292. bp represented two novel splice variants of the CTLA4 gene. A reduction in the frequency of mCTLA4-672. bp and sCTLA4-562. bp was observed in SLE and RA patients compared to healthy controls. The shortest splice variant, K-CTLA4-142. bp, was predominantly detected in all of the tested cohorts, while the decreased expression of the N-CTLA4-292. bp variant was observed in the autoimmune subjects. The exonic splice enhancer motifs of the SRp40 protein were found exactly at the splice junction of wCTLA4 (-ACAGAGC-, 2.7) and K-CTLA4 (-TGAAAAG-, 3.37), and that of the SRp55 protein was found at the splice junction of L-CTLA4 (-TGTGTG-, 2.82). Our study highlights the discrepancies in the expression spectrum of the CTLA4 gene in autoimmune patients and healthy subjects. The abnormal expression pattern of the CTLA4 gene in autoimmune patients suggests that in addition to allelic variation, the expression pattern of CTLA4 could contribute to autoimmunity.
KW - CTLA4
KW - HT
KW - RA
KW - SLE
KW - Splice variants
UR - http://www.scopus.com/inward/record.url?scp=84890426976&partnerID=8YFLogxK
U2 - 10.1016/j.gene.2013.10.034
DO - 10.1016/j.gene.2013.10.034
M3 - Article
C2 - 24498648
AN - SCOPUS:84890426976
VL - 534
SP - 307
EP - 312
JO - Gene
JF - Gene
SN - 0378-1119
IS - 2
ER -