Elsevier

Cytokine

Volume 160, December 2022, 156025
Cytokine

Genetic variation in C-reactive protein (CRP) gene is associated with retinopathy and hypertension in adolescents with type 1 diabetes

https://doi.org/10.1016/j.cyto.2022.156025Get rights and content

Highlights

  • We analyzed the c CRP gene polymorphism in patients with T1D.

  • CC genotype is associated with a decreased risk of T1D and hypertension.

  • CT genotype is associated with an increased risk of T1D but a decreased risk of retinopathy.

  • TT genotype is associated with an increased risk of retinopathy and hypertension.

  • T allele is associated with an increased risk of T1D and hypertension.

Abstract

Background and aims

Elevated concentration of CRP has been associated with the risk of diabetes as well as cardiovascular events and microvascular complications in T1D patients. We hypothesize that the +1846 C > T CRP gene polymorphism may have impact on the risk of T1D and/or its complications.

Methods

We have examined 400 young patients with T1D and 250 healthy age-matched controls. The +1846 C > T CRP gene polymorphism was genotyped by ARMS–PCR method. The analysis covers microvascular complications, concentrations of serum pro- and anti-inflammatory markers, adhesion molecules, proangiogenic factor as well as blood pressure.

Results

CT genotype (OR = 1.799) and T allele (OR = 1.733) are associated with increased risk of T1D, while CC genotype decreases the risk of this condition (OR = 0.458). Moreover, increased risk of hypertension corresponds with TT and T variant (OR = 3.116 and OR = 1.830, resp.) while CC genotype is decreasing the risk (OR = 0.547). Furthermore, CT variant is connected with lower risk of retinopathy (OR = 0.512) whereas TT variant decreases the risk of this complication (OR = 2.228). Our data also implies various effects of CRP +1846 C > T polymorphism on the inflammatory status of T1D patients.

Conclusions

Although further studies are required, the +1846 C > T CRP gene polymorphism could be considered a genetic marker to predict susceptibility to retinopathy and hypertension in T1D adolescents.

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).

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