Variation in the Dopamine-4-Receptor Gene in Patients with Type 1 Diabetes.

INTRODUCTION: Because dopaminergic signaling pathways are one of the regulators of autoimmunity, we hypothesize that the -521C>T DRD4 gene polymorphism may associate with the risk of diabetes mellitus type 1 (DM1) and its comorbidities. METHODS: In this case-control study, we have examined 300 patients with DM1 in comparison to 300 healthy age-matched controls. Utilizing the amplification refractory mutation system-polymerase chain reaction method, we have analyzed the -521C>T polymorphism of dopamine D4 receptor-encoding gene. Obtained results have been evaluated according to diabetes comorbidities, inflammatory markers, CD14++CD16-, and CD14+CD16+ monocyte subsets as well as lipid profile. RESULTS: The key results of our study are as follows: (1) CC genotype and C allele are associated with a reduced risk of DM1 development (OR = 0.593, p = 0.005 and OR = 0.725, p = 0.003, respectively), whereas TT genotype and T allele are associated with a higher risk of DM1 (OR = 1.408, p = 0.04 and OR = 1.380, p = 0.003, respectively); (2) CC genotype is associated with an increased risk of dyslipidemia and retinopathy in diabetic patients (OR = 2.376, p = 0.001 and OR = 2.111, p = 0.01, respectively); (3) CC genotype and C allele carriers had the highest frequency of pro-inflammatory CD16+ monocytes (p = 2*10-4 and 0.04, respectively); (4) the DRD4 -521C>T polymorphism modifies the inflammatory status as well as lipid profile in DM1 patients. CONCLUSION: Our data imply that the dopaminergic signaling pathways may play an important role in the etiology of DM1 as well as its comorbidities and will provide a new insight into the DM1 risk management. The -521C>T DRD4 gene polymorphism could be considered a genetic marker to predict susceptibility to DM1 as well as retinopathy and dyslipidemia progress in patients with already established disease.

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

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.

Cytokines and chemokines multiplex analysis in patients with low disease activity rheumatoid arthritis.

Rheumatoid arthritis is a severe chronic autoimmune disorder that results from pathological activation of immune cells and altered cytokine/chemokine network. The aim of our study was to evaluate concentrations of chosen cytokines and chemokines in blood sera and synovial fluid samples isolated from low disease activity rheumatoid arthritis (RA) patients and osteoarthritis (OA) sufferers. Blood sera and synovial fluid samples have been obtained from 24 OA and 14 RA patients. Cytokines/chemokines levels have been determined using a Milliplex® Map 38-plex human cytokine/chemokine magnetic bead-based panel (Merck Millipore, Germany) and Luminex® MAGPIX® platform (Luminex USA). Low disease activity RA patients showed altered concentration of numerous cytokine/chemokine when compared to OA controls-they were characterized by, inter alia, increased: eotaxin/CCL11 (p = 0.037), GRO/CXCL1 (p = 0.037), IL-2 (p = 0.013), IL-4 (p = 0.017), IL-7 (p = 0.003), IL-8 (p = 0.0007) and GM-CSF (p = 0.037) serum levels, whilst MDC/CCL22 concentration was decreased in this group (p = 0.034). Eotaxin/CCL11 (p = 0.001), GRO/CXCL1 (p = 0.041), IL-10 (p = 0.003), GM-CSF (p = 0.01), IL-1RA (p = 0.0005) and VEGF (p = 0.01) concentrations in synovial fluid of RA females were also increased. Even with low disease activity score, RA patients exhibited increased concentrations of cytokines with pro- and anti-inflammatory activities, as well as numerous chemokines, growth factors and regulators of angiogenesis. Surprisingly, RA subjects also shown decreased concentration of CCL22 chemokine. The attempt to restore cytokine balance and tolerogenic environment is ineffective in RA sufferers even with good disease management. Distinguished factors could serve as possible indicators of disease progression even in low disease activity patients.

CCR5-Δ32 polymorphism is a genetic risk factor associated with dyslipidemia in patients with type 1 diabetes.

AIM: In the currently available literature there are no works investigating the correlation between CCR5-Δ32 polymorphism and dyslipidemia in children with type 1 diabetes mellitus (T1D). Therefore, we have decided to explore the potential role played by this polymorphic locus in the incidence of dyslipidemia as an important risk factor for cardiovascular disease (CVD) in patients with T1D. METHODS: A total of 380 patients with T1D were selected. Patients were divided into two groups: 180 patients with diabetic dyslipidemia and 200 controls without dyslipidemia. Characterization of CCR5-Δ32 genotypes was analyzed by polymerase chain reaction. Logistic regression model was used to examine the association between CCR5-Δ32 polymorphism and dyslipidemia. RESULTS: When participants were analyzed according to CCR5-Δ32 polymorphism, Δ32 carriers presented higher levels of: HbA1c (p < 0.001), fasting plasma glucose (p < 0.001), LDL (p = 0.02) as well as TG (p = 0.01) and lower levels of HDL (p = 0.01) than noncarriers. Moreover, the minor allele Δ32 was more frequent in dyslipidemic subjects than controls (p < 0.001) and conferred an increased individual risk for dyslipidemia (OR = 2.327; 95% CI = 11.241-4.365; p = 0.009). CONCLUSIONS: The findings of our study suggest that the CCR5-Δ32 polymorphism is associated with elevated plasma lipid levels and the Δ32 allele increases the risk of dyslipidemia in patients with T1D. Identification of the functional variant underlying these associations may potentially lead to the development of a novel and adjunctive approach for the treatment of dyslipidemia and CVD.

The KL-VS polymorphism of KLOTHO gene is protective against retinopathy incidence in patients with type 1 diabetes.

BACKGROUND AND AIMS: KLOTHO is an anti-ageing circulating hormone involved in insulin signaling, inflammation and vascular homeostasis through its protective effects on the endothelium and antioxidant actions. The common functional "KL-VS" variant of the KLOTHO gene is reproducibly associated with longevity in humans. Large number of studies have evaluated close relationship between KLOTHO protein and diabetes but the association between KL-VS variant and retinopathy in type 1 diabetes mellitus (T1D) is unknown. Therefore, in the present study we examined the association between the KL-VS polymorphism and the risk of diabetic retinopathy (DR) in patients with T1D. METHODS: We examined 400 patients with T1D and 350 healthy age-matched controls. The analysis concerned KL-VS polymorphism along with the levels of serum inflammatory (CRP, TNF-α) and anti-inflammatory (IL-10) markers, pro-angiogenic (angiogenin) and anti-angiogenic interferon gamma-induced protein 10 (IP-10) factors as well as adhesion molecules (ICAM-1, ICAM-3). RESULTS: We did not find significant association between T1D and KL-VS alleles. However, we observed that the incidence of KL-VS genotype is lower in a group with retinopathy in comparison to diabetic patients without this complication. Moreover, we established that KL-VS carriers had the lowest levels of inflammatory markers, pro-angiogenic factors and adhesion molecules. Simultaneously, the KL-VS carriers had increased serum levels of anti-inflammatory and anti-angiogenic cytokines than holders bearing wild type genotype. CONCLUSIONS: In conclusion, the findings of our studies suggest that the functional KL-VS variant of the KLOTHO gene protects against the development of retinopathy in patients with T1D.

Circulating CD34+ and CD34+VEGFR2+ progenitor cells are associated with KLOTHO KL-VS polymorphism.

BACKGROUND: KLOTHO is a regulator of endothelial cells activity and integrity. It has been described for the first time because of its anti-aging properties. KLOTHO encoding gene is present in many functional variants in humans, including "KL-VS" variant that has been connected with longevity and cardiovascular disease development. Few mechanisms have been proposed to explain these associations, but none of them focused on cells from CD34+ population. The aim of our study was to investigate influence of KLOTHO KL-VS polymorphism on populations of CD34+ and CD34+VEGFR2+ cells. METHODS AND RESULTS: We examined 167 Polish subjects from Pomeranian region. The analysis concerned KL-VS polymorphism, flow cytometry evaluation of whole blood cells and determination of endothelium-associated serum/plasma factors. Our results indicate that individuals possessing at least one KL-VS allele are characterized by greater number of CD34+ and CD34+VEGFR2+ and their various subpopulations (CD34+CD133+, CD34+c-Kit+, CD34+CXCR4+ and CD34+VEGFR2+c-Kit+) than wild-type volunteers. This group also exhibited more favorable lipid profile and statistically insignificant decrease of vWF and angiotensin II in their blood, whereas VEGF levels were elevated. CONCLUSION: One of the mechanisms that are responsible for previously described KL-VS heterozygote advantage may be connected with maintaining greater size of hematopoietic and endothelial progenitor cells population.

Estrogen receptor α gene polymorphism and vascular complications in girls with type 1 diabetes mellitus.

The effect of estrogens is mediated by activation of estrogen receptors (ERs). Because ER-α gene polymorphisms may exert different effects in childhood, we analyzed the associations between the IVS1 -397T>C (PvuII) polymorphism and systemic inflammatory state, proangiogenic factors, frequency of monocyte subsets, lipid profile, blood pressure, and vascular complications in girls with type 1 diabetes mellitus (DM1). We examined 180 young girls with DM1 and 120 healthy age-matched controls. The analysis concerned PvuII polymorphism of the ER-α gene as well as the levels of serum inflammatory markers (CRP, IL-6, TNF-α), proangiogenic factors (VEGF, angiogenin), 17ß-estradiol, values of monocyte subsets (CD14++CD16- and CD14+CD16+), lipid profile, and blood pressure. In our study, girls with CC genotype had lower level of inflammatory and angiogenic factors and lower frequencies of CD14+CD16+ monocytes in comparison to CT or TT carriers. Simultaneously, the CC carriers had a greater population of CD14++CD16- monocytes, increased blood pressure, and serum levels of: estrogen, total cholesterol, triglycerides, and low-density lipoprotein cholesterol than girls bearing CT or TT genotype. Our study suggests a pleiotropic effect of PvuII polymorphic CC variant on diabetic vasculopathies. Although the CC genotype carriers demonstrate less inflammatory and angiogenic activity, they seem to display less favorable cardiometabolic features. Based on our study, we cannot distinguish PvuII ER-α genotype that could be useful in identification of DM1 girls that are more prone to develop of late vascular complications, before the occurrence of first clinical symptoms.

Sex-related association of serum uric acid with inflammation, kidney function and blood pressure in type 1 diabetic patients.

BACKGROUND/OBJECTIVE: Recent studies suggest that uric acid (UA) is a mediator of diabetic nephropathy. We hypothesized that serum UA would associate with the prevalence of diabetic nephropathy in youth with type 1 diabetes (T1D), and that this relationship would differ by sex. METHODS: We examined 120 young boys and the same number of girls with T1D. C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor α (TNF-α), UA, cystatin C serum concentrations, albumin excretion rate and blood pressure were also analyzed. RESULTS: T1D boys had higher serum UA and creatinine concentration, as well as albumin excretion rate and estimated glomerular filtration rate than T1D girls. Moreover, newly diagnosed nephropathy was more common in male subjects in comparison to female patients. Only in T1D boys serum UA was positively correlated with concentrations of subclinical inflammatory markers (CRP, IL-6, TNF-α), the indicators of renal function (albumin excretion rate, serum cystatin C level), blood pressure and negatively correlated with anti-inflammatory IL-10. In addition, only in T1D girls serum UA concentration was negatively correlated with hemoglobin A1c. CONCLUSIONS: Serum UA is associated with nephropathy prevalence, albeit only in boys with T1D and may be an important risk factor for predicting diabetes-related cardiorenal complications in these patients.

The GA genotype of the -1154 G/A (rs1570360) vascular endothelial growth factor (VEGF) is protective against hypertension-related chronic kidney disease incidence.

Vascular endothelial growth factor (VEGF) is a highly specific mitogen with angiogenic and vascular permeability activities for endothelial cells. VEGF participates in maintaining the renal vasculature integrity. There is no doubt that hypertension accelerates progression to renal dysfunction, resulting in chronic kidney disease (CKD). The purpose of our study was to examine the VEGF -1154 G/A (rs1570360) polymorphism among hypertensive patients with CKD. Additionally markers of endothelial damage have been related to the advancement of CKD. There were 96 consecutively admitted hypertensive patients referred to our Institution by their general practitioner. The patients were treated with an anti-hypertensive polytherapy. Ninety-nine healthy volunteers were enrolled as the control group. Our study revealed that both healthy and hypertensive groups frequencies of the genotypes varied significantly (p = 0.030, χ (2) test). The GA genotype frequency was significantly lower among patients in comparison with healthy. The presence of GA genotype was connected with a decreased risk of hypertension disease (OR = 0.48, p = 0.01). The VEGF -1154 GA carriers have been associated with the lowest values of Endostatin (p = 0.020), Angiogenin (p = 0.040) as well as vWf (p = 0.005). The GA genotype has been characterized by the highest values of eGFR (p = 0.024) and the lowest values of creatinine (p = 0.028) and BUN (p = 0.012). It is evident that the GA genotype of VEGF polymorphism localized at -1154 position is a genetic protective factor for development arterial hypertension and is associated with less progressed CKD.

The GG genotype of the -152 G/A vascular endothelial growth factor (VEGF) polymorphism predisposes to hypertension-related chronic kidney disease.

Our purpose was to determine whether the VEGF -152 G/A polymorphism could be associated with chronic kidney disease and endothelial dysfunction in hypertensive patients. There were 100 healthy volunteers enrolled into the control group. The group of patients was constituted by 99 consecutively admitted hypertensive patients referred to our Institution by their general practitioner. All patients were treated with anti-hypertensive polytherapy. Presented study revealed that the hypertensive patients bearing the GG genotype were characterized by the highest values of diastolic blood pressure and markers of endothelial damage such as Angiogenin, Endostatin, CRP as well as von Willebrandt factor. In addition, higher number of immature endothelial progenitor cells with CD34(+)CD133(+), CD34(+)CD133(-) markers was observed in GG hypertensive carriers while in normotensive individuals no differences were found. Such phenomenon may indicate an increased mobilization of bone-marrow derived endothelial progenitors. It may testify to the preserved compensatory mechanism in chronic kidney disease (CKD) patients until the G3a stage of the disease. Moreover, patients with higher estimated glomerular filtration rate (eGFR) level had lower of vWf and Endostatin values, and higher level of VEGF. Taken together our findings clearly indicate the -152 GG hypertensive carriers as more prone to develop CKD. We can suspect that the VEGF -152 GG genotype is strongly associated with hypertension-dependent CKD.

IL-33 Effect on Quantitative Changes of CD4+CD25highFOXP3+ Regulatory T Cells in Children with Type 1 Diabetes.

IL-33 is an IL-1 cytokine family member, with ability to induce both Th1 and Th2 immune responses. It binds to ST2 receptor, whose deficiency is associated with enhanced inflammatory response. The most recent studies have shown the immunoregulatory effect of IL-33 on Tregs in animal models. As type 1 diabetes is an autoimmune, inflammatory disease, where Treg defects have been described, we aimed to analyze the in vitro influence of recombinant IL-33 on quantitative properties of regulatory CD4+CD25highFOXP3+ T cells. CD4+CD25highFOXP3+ as well as CD4+CD25highFOXP3+ST2+ Tregs were analyzed by flow cytometry. In a group of patients with type 1 diabetes in vitro IL-33 treatment induced regulatory CD4+CD25highFOXP3+ cell frequencies as well as upregulating the surface expression of ST2 molecule. In addition, the number of CD4+CD25highFOXP3+ cells carrying ST2 receptor increased significantly. Similar effect was observed in case of the FOXP3 expression. We did not observe any significant changes in IL-33 treated cells of healthy controls. The level of ST2 was higher in serum of patients with type 1 diabetes in comparison to their healthy counterparts. We propose that IL-33 becomes an additional immunostimulatory factor used to induce Treg expansion in future clinical trials of adoptive therapy in type 1 diabetes.

Vascular endothelial growth factor polymorphism (-460 T/C) is related to hypertension-associated chronic kidney disease.

Our aim was to characterize the endothelial progenitor cells (EPCs) in normotensive controls and treated hypertensive individuals within the vascular endothelial growth factor (VEGF) -460 C/T polymorphism as well as to investigate whether this polymorphism predisposes to hypertension-related chronic kidney disease. The hypertensive patients bearing the TT genotype had the highest levels of immature EPC with the following phenotypes: CD34(+), CD34(+)CD45(dim), CD34(+)CD133(+)CD45(dim). The study showed the estimated glomerular filtration rate values significantly lower and creatinine and BUN parameters higher among the TT hypertensive patients. We presume that the highest mobilization of EPCs from bone marrow may signalize more severe renal hypertension-related complications in the VEGF -460 TT genotype.

Associations of the obesity gene FTO variant with complications and comorbidities in patients with type 1 diabetes.

BACKGROUND AND AIMS: Because FTO gene is connected with the risk of obesity, cardiovascular disease and hypertension, as well as type 2 diabetes, we hypothesize that the rs9939609 FTO polymorphism may affect type 1 diabetes (T1D) complications and comorbidities. METHODS: We have investigated the associations of the FTO gene variant with the T1D and its complications and comorbidities, as well as the serum levels of pro- and anti-inflammatory markers and lipid profiles. RESULTS: The key results of our study are as follows: (1) the rs9939609 FTO polymorphism does not predispose individuals to T1D; (2) AA genotype is associated with an increased risk of overweight and obesity, retinopathy, hypertension, dyslipidemia and celiac disease; (3) AT genotype is associated with a decreased risk of retinopathy and celiac disease, whereas TT genotype is connected with decreased risk of dyslipidemia; (4) the FTO rs9939609 polymorphism affects the inflammatory status as well as lipid profile in T1D patients. CONCLUSIONS: Our results, for the first time, comprehensively indicate that the rs9939609 FTO polymorphism could be considered a genetic marker for increased susceptibility to T1D complications and comorbidities as well as suggests importance of FTO-mediated pathways in their etiology.

The serum IL-6 profile and Treg/Th17 peripheral cell populations in patients with type 1 diabetes.

IL-6 is a pleiotropic cytokine involved in the regulation of the immune response, inflammation, and hematopoeisis. Its elevated levels are found in a range of autoimmune and chronic inflammatory diseases. IL-6 is also involved in regulation of the balance between two T cell subsets: Tregs and Th17, which have contradictory functions in the control of inflammation. The present study provides a quantitative analysis regarding the Th17/Treg cell balance in peripheral blood of children with type 1 diabetes and its association with serum IL-6 level.

Associations of TP53 codon 72 polymorphism with complications and comorbidities in patients with type 1 diabetes.

Wild-type TP53 plays an important role in the regulation of immune response and systemic inflammation. In type 1 diabetes (T1D), TP53 pathways are upregulated and an increased susceptibility to apoptosis is observed. We hypothesize that TP53 codon 72 polymorphism could be associated with complications and comorbidities in patients with T1D. We have investigated the associations of the TP53 codon 72 polymorphism with the T1D complications and comorbidities (retinopathy, nephropathy, hypertension, dyslipidemia, autoimmune thyroiditis, and celiac disease) in 350 patients. The key results of our approach are as follows: (1) In diabetic subjects, the Pro/Pro genotype is associated with an increased risk of microvascular complications, dyslipidemia, and celiac disease; (2) the Arg/Arg variant is associated with a decreased risk of autoimmune thyroiditis and celiac disease; (3) the Pro allele is associated with an increased risk of dyslipidemia, autoimmune thyroiditis, and celiac disease. Although further studies are required, our results for the first time indicate that the TP53 codon 72 polymorphism could be considered a genetic marker to predict the increased susceptibility to some T1D complications and comorbidities. KEY MESSAGES: We analyzed the TP53 codon 72 polymorphism in patients with T1D. Pro/Pro genotype is associated with an increased risk of microvascular complications, dyslipidemia, and celiac disease. The Arg/Arg variant is associated with a decreased risk of autoimmune thyroiditis and celiac disease. The Pro allele is associated with an increased risk of dyslipidemia, autoimmune thyroiditis, and celiac disease.

A new potential mode of cardiorenal protection of KLOTHO gene variability in type 1 diabetic adolescents.

As the KL-VS haplotype alters secretion and activity of KLOTHO and uric acid (UA) is associated with endothelial dysfunction and inflammation, their mutual links may contribute to microalbuminuria (MA) in patients with type 1 diabetes (T1D). Therefore, we hypothesize that KL-VS polymorphism could be associated with the prevalence of MA in T1D patients, and KL-VS polymorphism could modify physiological functions and pathogenic potential of UA. We have examined 350 patients with T1D. The analysis concerned KL-VS polymorphism along with the concentrations of serum inflammatory markers, indicators of renal function, blood pressure, and lipid profile. The incidence of KL-VS genotype was lower in a group with MA in comparison to patients without this condition. Moreover, KL-VS carriers had improved indicators of renal function, lower concentrations of pro-inflammatory cytokines, and higher levels of anti-inflammatory markers. Simultaneously, among KL-VS carriers serum UA was negatively correlated with HbA1c, albumin excretion rate, ACR, CRP, TNF-α, total cholesterol, LDL-C and triglycerides, and positively correlated with HDL-C. Moreover, among wild-type KLOTHO carriers serum, UA was in positive correlation with creatinine, blood pressure, IL-12 and MCP-1, and in negative correlation with IL-10 and eGFR. Findings of our study suggest that the functional KL-VS polymorphism is independently associated with MA and the KL-VS genotype protects from the development of MA, and KL-VS polymorphism may modify physiological functions and pathogenic potential of UA by altering the levels of HbA1c, inflammatory biomarkers, indicators of renal function, blood pressure, and lipid profile. KEY MESSAGES: • We analyzed the KL-VS polymorphism and the UA serum level in patients with T1D. • The KL-VS polymorphism is independently associated with microalbuminuria. • The KL-VS alleles protect from the development of microalbuminuria. • KL-VS polymorphism may modify physiological functions and pathogenic potential of uric acid.

New mechanisms of CCR5-Δ32 carriers' advantage - Impact on progenitor cells and renal function.

BACKGROUND: CCR5 is a chemokine receptor expressed by various populations including leukocytes, smooth muscle cells and endothelium. Δ32 polymorphism of CCR5 gene has been connected with, inter alia, cardiovascular disease development. The aim of our study was to evaluate impact of CCR5 variant on CD34+ and CD34+VEGFR2+ cells - populations involved in cardiovascular system homeostasis and regeneration. METHODS AND RESULTS: We have examined 170 Polish subjects from Pomeranian region. The analysis concerned CCR5 polymorphism and flow cytometry evaluation of whole blood cells. Our results indicate that individuals with at least one CCR5-Δ32 allele are characterized by greater number of CD34+CXCR4+, CD34+VEGFR2+ and CD34+VEGFR2+c-Kit + cells than their wild type counterparts. This group also exhibits more beneficial values of renal function parameters. CONCLUSION: Maintaining greater size of CD34+ and CD34+VEGFR2+ populations as well as proper kidney function may constitute mechanisms that connect chemokine receptor polymorphism with cardiovascular system health.

CD34+ and CD34+VEGFR2+ cells in poorly controlled hypertensive patients.

CD34+ and CD34+VEGFR2+ cells participate in the repair of damaged endothelium and vascular remodelling. As their number and activity change due to the development of cardiovascular diseases, they are recognised as useful markers of cardiovascular health. As ineffective blood pressure control concerns high percentage of hypertensive patients, the purpose of our study was to investigate if proportions of various CD34+ and CD34+VEGFR2+ populations change due to hypertension occurrence and the effectiveness of the therapy. We also wanted to establish which factors impact these cells. Circulating populations of CD34+ and CD34+VEGFR2+ cells were analysed in peripheral blood samples by flow cytometry. Serum/plasma levels of sICAM-1, sVCAM-1 and vWF were determined using immunoenzymatic assay. We did not observe differences in CD34+ populations, but proportions of CD34+VEGFR2+ (p = 0.006), CD34+VEGFR2+CD133+ (p = 0.002) and CD34+VEGFR2+c-Kit+ (p = 0.003) cells were reduced in patients with poorly controlled blood pressure. We have also established that these cells exhibit connections with age, blood pressure and sICAM-1 serum levels. However, multiparametric regression analyses did not indicate any of the analysed variables as independent factors affecting CD34+VEGFR2+ populations. CD34+VEGFR2+, CD34+VEGFR2+CD133+ and CD34+VEGFR2+c-Kit+ cells are reduced in poorly controlled hypertensive patients, which may be partially connected with increased cardiovascular complications and mortality observed in this group.

CCR5-Δ32 gene polymorphism is associated with retinopathy in patients with type 1 diabetes.

AIM: The aim of the study was to assess the relationship between the CCR5-Δ32 polymorphism and the risk of diabetic retinopathy (DR) in patients with DM1. METHODS: We examined 420 patients and 350 healthy controls. The analysis concerned CCR5-Δ32 polymorphism as well as levels of serum inflammatory markers (CRP, TNF-α), adhesion molecules (VCAM, ICAM-1, ICAM-3) and CCR5 ligand (MCP-1). RESULTS: We found a negative association between DM1 and Δ32 allele. Moreover, the frequency of Δ32 allele was higher in a group with DR in comparison to control subjects without this complication. We also found that Δ32 carriers had the highest levels of: HbA1c, inflammatory markers, adhesion molecules and CCR5 ligand. CONCLUSIONS: The findings of our studies suggest that the CCR5-Δ32 polymorphism is associated with DM1 such that the Δ32 allele protects against the development of DM1 and increases the risk of DR in patients who have already developed the disease.

Association of circulating progenitor cells with angiotensin II in newly diagnosed hypertensive patients.

Populations of CD34- and VEGFR2-expressing cells are responsible for regeneration of damaged endothelium and vascular remodelling. As their quantity and activity changes during cardiovascular diseases, they are potentially useful markers of cardiovascular health. The aim of our study was to investigate changes of various CD34+ and CD34+ VEGFR2+ populations in subjects with newly recognised hypertension and to evaluate whether observed alterations are influenced by clinical parameters and angiotensin II. Circulating CD34+ and CD34+ VEGFR2+ cells were analysed in peripheral blood samples by flow cytometry. Serum levels of angiotensin II were determined using immunoenzymatic assay. We discovered increased proportions of various CD34+ populations and CD34+ VEGFR2+ c-Kit+ cells in newly diagnosed patients. CD34+ cells seem to be influenced by angiotensin II, but we did not observe comparable results when populations co-expressing VEGFR2 were analysed. The quantity of CD34+ VEGFR2+ cells in patients with newly recognised primary hypertension ought to be determined by other factors. Increased proportions of CD34+ progenitors in blood could comprise compensatory mechanism for increased endothelial damage in hypertension.