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CXCL4L1 Promoter Polymorphisms Are Associated with Improved Renal Function in Type 1 Diabetes
Tabea Armbrust1, Meredith Paige Millis2, Maria Lucrecia Alvarez2
1Department of Geriatric Medicine, RWTH University Hospital, 52074 Aachen, Germany.
Journal of Immunology (Baltimore, Md. : 1950)
|December 30, 2018
Summary
Genetic variants in the CXCL4L1 promoter may protect against diabetic kidney disease. These variants increase CXCL4L1 expression, activating anti-inflammatory factors and reducing renal inflammation in type 1 diabetes.
Area of Science:
- Nephrology
- Genetics
- Immunology
Background:
- Inflammation plays a key role in diabetic kidney disease pathogenesis.
- Genetic factors influencing inflammatory gene expression may increase susceptibility to diabetic renal complications.
Purpose of the Study:
- To investigate associations between genetic variants in inflammatory genes and renal function in type 1 diabetes.
- To explore the role of CXCL4L1 in high glucose-induced renal inflammation.
Main Methods:
- Genomic analysis of 55 variants in 16 inflammatory genes in 1540 participants.
- Reporter gene assays to assess promoter activity.
- Overexpression and knockdown studies in human mesangial cells.
Main Results:
- Three CXCL4L1 promoter variants (rs872914/A, rs941757/G, rs941758/A) showed protective associations with renal function.
- These variants enhanced CXCL4L1 promoter activity.
- High glucose increased CXCL4L1 expression, which upregulated anti-inflammatory factors SMAD7 and IκBα.
Conclusions:
- CXCL4L1 promoter variants may offer protection against diabetic kidney inflammation.
- Increased CXCL4L1 expression, driven by these variants, activates anti-inflammatory pathways in mesangial cells.
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