Genetic variation in C-reactive protein (CRP) gene is associated with retinopathy and hypertension in adolescents with type 1 diabetes
Introduction
Type 1 diabetes (T1D) is a proinflammatory state typified by increased C-reactive protein (CRP) levels, endothelial dysfunction and increasing risk of cardiovascular disease [1], [2]. Accumulating evidence indicates that inflammation plays an important role in the pathogenesis of diabetes [3] and its complications [4]. Concentration of circulating CRP, a very sensitive marker of systemic inflammation, has been associated with the risk of diabetes by numerous studies in the various cohorts [5]. Several investigations have also identified higher levels of CRP as a risk factor for cardiovascular events in T1D patients [6] and the progression of diabetes complications [7].
CRP levels display extensive interindividual variability. Although plasma CRP concentrations are influenced by the combination of sociodemographic, behavioral and lifestyle factors as well as obesity and prevalent diabetes, family [8] and twin [9] studies have demonstrated that CRP levels are substantially (35–40 % and 40–62 % resp.) determined by heritable factors. Several investigations have also shown that CRP single nucleotide polymorphisms (SNPs) might affect serum CRP levels [10], [11]. The +1846 C > T CRP gene polymorphism (rs1205) has been connected with concentration of circulating CRP and indicated as likely affecting gene expression [12].
Therefore, it is plausible that genetic variants of CRP have impact on the risk of T1D and/or its complications. In the current study we have investigated the association between the +1846 C > T CRP gene polymorphism and microvascular complications in T1D adolescents.
Section snippets
Subjects
This study was conducted on 400 Caucasoid adolescents including 196 boys and 204 girls (mean age 15.6 ± 3.1 years) with clinical and laboratory diagnosis of T1D, recruited from the Chair and Clinics of Pediatrics, Diabetology and Endocrinology, Medical University of Gdańsk. T1D diagnosis was based on the American Diabetes Association criteria [13]. All patients were treated with humanized insulin at doses of 0.87 ± 0.2 U/kg. At the time of sample collection biochemical measurement of renal
The +1846 C > T CRP genotype distribution
The +1846 C > T CRP genotypes were analyzed in T1D patients and healthy controls. The occurrence of each genotype and allele frequencies is shown in Table 1. The genotype distributions (for both, healthy group and T1D patients) were in Hardy-Weinberg equilibrium (p = 0.76 and 0.64, resp.). Comparison of the frequencies of CRP +1846 C > T genotypes between healthy group and the T1D patients revealed significant differences (p < 0.000). The presence of CC variant was connected with an nearly
Discussion
In the present study, we have investigated the association between the +1846 C > T CRP gene polymorphism and microvascular complications in T1D adolescents. Only few studies have examined the connection between this polymorphism and type 2 diabetes (T2D), but have produced divergent data and no direct evidence for a functional role of SNP has been provided [17], [18], [19], [20]. The study of the relationship between this CRP variant with T1D complications such as retinopathy and nephropathy as
CRediT authorship contribution statement
Bartosz Słomiński: Conceptualization, Methodology, Writing – original draft. Martyna Jankowiak: Investigation. Agata Maciejewska: Investigation. Maciej Studziński: Investigation. Aleksandra Mączyńska: Investigation. Maria Skrzypkowska: Writing – review & editing. Magdalena Gabig-Cimińska: Formal analysis. Małgorzata Myśliwiec: Funding acquisition.
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgments
This work was supported by The State Committee for Scientific Research ST49 (Medical University of Gdańsk).
References (25)
- et al.
Familial and genetic determinants of systemic markers of inflammation: the NHLBI family heart study
Atherosclerosis
(2001) - et al.
Polymorphisms within the C-reactive protein (CRP) promoter region are associated with plasma CRP levels
Am. J. Hum. Genet.
(2005) - et al.
C-reactive protein gene polymorphisms, C-reactive protein blood levels, and cardiovascular disease risk
J. Am. Coll. Cardiol.
(2007) - et al.
C-reactive protein gene variation and type 2 diabetes mellitus: a case-control study
Atherosclerosis
(2008) - et al.
DCCT/EDIC Group of Investigators, The predictive role of markers of Inflammation and endothelial dysfunction on the course of diabetic retinopathy in type 1 diabetes
J. Diabetes Complications
(2015) - et al.
CRP polymorphisms and DNA methylation of the AIM2 gene influence associations between trauma exposure, PTSD, and C-reactive protein
Brain Behav. Immun.
(2018) - et al.
CCR5-Δ32 gene polymorphism is associated with retinopathy in patients with type 1 diabetes
Mol. CellEndocrinol.
(2017) - et al.
Plasma concentration of C-reactive protein is increased in type I diabetic patients without clinical macroangiopathy and correlates with markers of endothelial dysfunction: evidence for chronic inflammation
Diabetologia
(1999) - et al.
National Heart, Lung, and Blood Institute & National Institute of Diabetes and Digestive and Kidney Diseases Working Group on Cardiovascular Complications of Type 1 Diabetes Mellitus, Report of the National Heart, Lung, and Blood Institute-National Institute of Diabetes and Digestive and Kidney Diseases Working Group on Cardiovascular Complications of Type 1 Diabetes Mellitus
Circulation
(2005) - et al.
The Role of Inflammation in Diabetes: Current Concepts and Future Perspectives
Eur. Cardiol.
(2019)