Vitamin D Metabolites and IL1β RS16944 Polymorphism in Type 2 Diabetes Patients: Evidence for Functional Interaction

Presentation Number: SUN 331
Date of Presentation: April 2nd, 2017

Nojan Nejatian1, Marissa Penna-Martinez2 and Klaus Badenhoop*3
1University Hospital Frankfurt am Main, Germany, 2University Hospital, Goethe-University Frankfurt am Main, Germany, 3Goethe-University Hospital, Frankfurt, Germany


Introduction: High levels of circulation Interleukin 1β (IL1β) are associated with the risk of developing type 2 diabetes (T2D). Furthermore increased levels of IL1β in nondiabetic offspring of T2D patients confer susceptibility for the metabolic syndrome. Recent studies suggest that a vitamin D deficiency and genetic variation in the IL1β gene are associated with both prediabetes and prevalent diabetes. The single nucleotide polymorphism (SNP) rs16944 in the promotor region of the IL1β gene may modulate the IL1β production, which could be downregulated by vitamin D metabolites. For this purpose we investigated this SNP rs16944 in German patients with T2D and healthy controls (HC) and correlated the findings with concentrations of vitamin D metabolites.

Methods: 504 T2D patients and 447 HC were genotyped for the IL1β SNP rs16944 by a Taqman assay. Additionally 25(OH)D3 and 1,25(OH)2D3 plasma levels of 76 T2D patients and 267 HC were measured by radioimmunoassay. Statistical analyses were performed using allele-wise and genotype-wise chi(x)2-tests. Associations between 25(OH)D3 genotypes and vitamin D levels were analyzed by Kruskal-Wallis-tests.

Results: The homozygous AA genotype of IL1ß SNP rs16944 was significantly less frequent in T2D compared to HC whereas homozygous GG and heterozygous AG genotypes were more frequent in T2D (AA: 48.5 vs. 37.95%; AG 40vs. 49.7%; GG: 11.4vs. 12.4%; p=0.003). Furthermore the allele A was less (68.6 vs. 62.7% OR=0.77; 95% CI: 0.64-0.93) and allele G was more frequent (31.4 vs. 37.3% OR=1.3 95% CI: 1.07-1.57, p=0.008) in T2D patients compared to HC. Both T2D patients and HC with IL1β genotypes AA and AG did not differ for the vitamin D metabolites. However T2D patients with the GG genotype showed significantly lower levels of 25(OH)D3 (median 34.95 vs. 13.7 ng/ml p= 9x10-6) and 1,25(OH)2D3  (median 59.05 vs. 41.15 pg/ml p=0.006) compared to HC with the same genotype.

Conclusion: We describe an association of the IL1β SNP rs16944 with T2D in German patients. In addition, significantly lower 25(OH)D3 and 1,25(OH)2D3 levels were observed in T2D patients with the GG genotype. Whereas the major allele A appears to be protective, the minor allele G is may predispose to T2D in combination with a vitamin D deficiency. Our results suggest that vitamin D deficiency enhances the genetic risk for T2D conferred by the genotype GG of IL1β SNP rs16944. Whether and how vitamin D interacts with IL1β through this polymorphism is subject to further studies.


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