A Graves’ Disease-Associated Kozak Sequence Single-Nucleotide Polymorphism Enhances the Efficiency of CD40 Gene Translation: A Case for Translational Pathophysiology
-
- Eric M. Jacobson
- Division of Endocrinology, Diabetes, and Bone Disease, Department of Medicine (E.M.J., E.C., Y.T.), Mount Sinai School of Medicine, New York, New York 10029
-
- Erlinda Concepcion
- Division of Endocrinology, Diabetes, and Bone Disease, Department of Medicine (E.M.J., E.C., Y.T.), Mount Sinai School of Medicine, New York, New York 10029
-
- Taiji Oashi
- Department of Physiology and Biophysics (T.O.), Mount Sinai School of Medicine, New York, New York 10029
-
- Yaron Tomer
- Division of Endocrinology, Diabetes, and Bone Disease, Department of Medicine (E.M.J., E.C., Y.T.), Mount Sinai School of Medicine, New York, New York 10029
書誌事項
- 公開日
- 2005-06-01
- DOI
-
- 10.1210/en.2004-1617
- 公開者
- The Endocrine Society
この論文をさがす
説明
<jats:title>Abstract</jats:title><jats:p>We analyzed the mechanism by which a Graves’ disease-associated C/T polymorphism in the Kozak sequence of CD40 affects CD40 expression. CD40 expression levels on B cells in individuals with CT and TT genotypes were decreased by 13.3 and 39.4%, respectively, compared with the levels in CC genotypes (P = 0.012). Similarly, Rat-2 fibroblasts transfected with T-allele cDNA expressed 32.2% less CD40 compared with their C-allele-transfected counterparts (P = 0.004). Additionally, an in vitro transcription/translation system showed that the T-allele makes 15.5% less CD40 than the C-allele (P < 0.001), demonstrating that the effect of the single-nucleotide polymorphism (SNP) on CD40 expression is at the level of translation. However, the SNP did not affect transcription, because the mRNA levels of CD40, as measured by quantitative RT-PCR, were independent of genotype. Therefore, our results may suggest that the C allele of the CD40 Kozak SNP, which is associated with Graves’ disease, could predispose to disease by increasing the efficiency of translation of CD40 mRNA.</jats:p>
収録刊行物
-
- Endocrinology
-
Endocrinology 146 (6), 2684-2691, 2005-06-01
The Endocrine Society
