کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5509621 | 1538628 | 2017 | 40 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
3â²-UTR SNP rs2229611 in G6PC1 affects mRNA stability, expression and Glycogen Storage Disease type-Ia risk
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
The frequency of rs2229611, previously reported in Chinese, Caucasians, Japanese and Hispanics, was investigated for the first time in Indian ethnicity. We analyzed its role in the progression of Glycogen Storage Disease type-Ia (GSD-Ia) and breast cancer. Genotype data on rs2229611 revealed that the risk of GSD-Ia was higher (PÂ =Â 0.0195) with CC compared to TT/TC genotypes, whereas no such correlation was observed with breast cancer cases. We observed a strong linkage disequilibrium (LD) among rs2229611 and other disease causing G6PC1 variants (|Â Dâ²|Â =Â 1, r2Â =Â 1). Functional validation performed in HepG2 cells using luciferase constructs showed significant (PÂ <Â 0.05) decrease in expression than wild-type 3â²-UTR due to curtailed mRNA stability. Furthermore, AU-rich elements (AREs) mediated regulation of G6PC1 expression characterized using 3â²-UTR deletion constructs showed a prominent decrease in mRNA stability. We then examined whether miRNAs are involved in controlling G6PC1 expression using pmirGLO-UTR constructs, with evidence of more distinct inhibition in the reporter function with rs2229611. These data suggests that rs2229611 is a crucial regulatory SNP which in homozygous state leads to a more aggressive disease phenotype in GSD-Ia patients. The implication of this result is significant in predicting disease onset, progression and response to disease modifying treatments in patients with GSD-Ia.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Clinica Chimica Acta - Volume 471, August 2017, Pages 46-54
Journal: Clinica Chimica Acta - Volume 471, August 2017, Pages 46-54
نویسندگان
Sellamuthu Karthi, Mohan Rajeshwari, Amirtharaj Francis, Matheshwaran Saravanan, Perumal Varalakshmi, Henry Houlden, Kumarasamy Thangaraj, Balasubramaniem Ashokkumar,