MMP9 Gene Polymorphism (rs3918242) Increases the Risk of Cardiovascular Disease in Type 2 Diabetes Patients.

Matrix metalloproteinase 9 (MMP-9) C(-1562)T gene polymorphism has been considered a risk factor for cardiovascular disease (CVD). Our study aimed to evaluate the association between this polymorphism and CVD in diabetes patients. The genotyping was performed in 740 patients with T2DM and 400 healthy subjects. A significant difference in the polymorphism distribution was revealed between patients and controls. The T allele and TT homozygote were associated with increased risk of diabetes (OR 1.88, p < 0.0001 and OR 3.77, p = 0.0002, respectively). The comparison between CVD+ and CVD- subgroups showed a much higher frequency of the T allele in patients with CVD (OR 2.87, 95% CI 2.14-3.85, p < 0.0001). Patients with the TT genotype had a higher prevalence of CVD (OR 3.19, 95% CI 1.55-6.56, p = 0.0015). The carrier genotypes (CT/TT) were correlated with HDL levels in both CVD+ and CVD- subgroups (p < 0.001 for both). In the logistic regression analysis, only C(-1562)T SNP was a significant predictor of CVD in diabetic patients (p < 0.001). In conclusion, our study suggests an association between MMP-9 C(-1562)T polymorphism and an increased risk of CVD in T2DM. If replicated in other studies, it could be considered a genetic marker for predicting risk of T2DM and its cardiovascular comorbidity.

Leu72Met Polymorphism in Ghrelin Gene: A Potential Risk Factor for Hypertension in Type 2 Diabetes Patients.

Objective: Ghrelin (GHRL) is known to be engaged in metabolic and cardiovascular processes. There is evidence suggesting its involvement in the regulation of blood pressure and hypertension. The purpose of this preliminary case-control study was to determine the involvement of the Leu72Met (rs696217) polymorphism in the GHRL gene in type 2 diabetes (T2DM). Methods: The Leu72Met polymorphism was genotyped in 820 individuals with T2DM and 400 healthy subjects by the PCR-RFLP technique. The polymorphism distribution was first compared in those withT2DM and controls, then in subgroups of participants representing different clinical phenotypes. Results: No significant association was identified between Leu72Met and T2DM. The distribution of polymorphism was analyzed in subgroups of individuals with different clinical phenotypes (hypertension, diabetic nephropathy, obesity). In this analysis, rs696217 was associated with hypertension. The presence of T allele was associated with higher risk of hypertension (OR = 2.50, 95% CI 1.68-3.73, p < 0.001). When adjusted for age, gender and BMI, the association was still significant (OR = 2.62, 95% CI 1.83-3.96, p < 0.001). A post hoc power calculations based on a minor allele frequency revealed the power of 97% for comparison between HY+ and HY- subgroups. Conclusion: This is the first study demonstrating that the ghrelin Leu72Met SNP is associated with hypertension in Caucasians with T2DM. If confirmed in larger studies in different populations, it may be a novel potential risk factor for hypertension in individuals withT2DM.

Apolipoprotein A5 gene polymorphism (rs662799) and cardiovascular disease in end-stage kidney disease patients.

BACKGROUND: Plasma triglyceride (TG) levels are a significant risk factor for cardiovascular disease (CVD). The APOA5 gene is one of the crucial factors in plasma TG metabolism regulation. The rs662799 polymorphism in the APOA5 gene has been reported to be associated with cardiovascular disease. The goal of this study was to evaluate the potential association of this variant with CVD in patients with end-stage kidney disease.  METHODS: In this case-control study the polymorphism was analyzed using the PCR-RFLP method in 800 consecutive patients with ESKD and 500 healthy controls. The genotype and allele distribution was compared between subgroups of patients with CVD (552) versus those without CVD (248). RESULTS: The frequency of the minor allele (C) in the healthy individuals was 9% compared to 12% in ESRD group (p = 0.09). The difference between groups was slightly higher for CC homozygote (3.5% versus 1.6%, p = 0.042). The ESKD patient group was analyzed according to the presence or absence of CVD. The significant differences in the polymorphism distribution were revealed in this analysis. The frequency of the C allele in the CVD + subgroup was 14% compared to 6% in CVD- patients (p = 0.001). In the CVD + subgroup the ORs (95% CI) for the C allele and CC genotype were 2.41 (1.61-3.6), p < 0.001 and 3.13 (1.07-9.14), p = 0.036, respectively. This indicates to the association of the variant C allele with cardiovascular disease in ESKD patients. The CC homozygotes have a threefold higher odds of CVD compared to TT homozygotes. The highest frequency of the C allele (18%) was observed in subgroup of patients with diabetic nephropathy, with OR (95% CI) 3.40 (2.13-5.43), p < 0.001.The presence of minor allele (CC and CT genotypes) was significantly associated with increased plasma triglyceride levels (p < 0.001 for both CVD + and CVD- groups). CONCLUSION: The present study demonstrated the effect of rs662799 polymorphism on plasma TG levels and its association with the development of cardiovascular disease in ESKD patients.

Arginase Gene Polymorphism Increases Risk of Diabetic Retinopathy in Type 2 Diabetes Mellitus Patients.

Studies have demonstrated that polymorphic variants of arginase 1 gene (ARG1) are involved in human diseases, such as coronary heart disease, hypertension, and diabetes. Our study aimed to investigate the association between ARG1 rs2781666 single nucleotide polymorphism (SNP) and diabetic retinopathy (DR) in type 2 diabetes (T2DM) patients. Polymorphism was genotyped in 740 T2DM patients and 400 healthy individuals. A significant difference in the genotype distribution was observed between the patients and the controls. The T allele and TT genotype were associated with an increased risk of T2DM (OR 1.4, 95% CI 1.14-1.72, p = 0.001 and OR 2.16, 95% CI 1.23-3.80, p = 0.007, respectively). When the T2DM subjects were stratified into DR+ and DR- subgroups, the T allele and TT genotype frequencies were significantly higher in the DR+ group compared to the DR- group, demonstrating OR 1.68 (1.33-2.12), p < 0.0001 and OR 2.39 (1.36-4.18), p = 0.002, respectively. Logistic regression analysis was applied to determine the interaction between the ARG1 genotypes and other risk factors. Only ARG1 rs2781666 SNP was a significant risk predictor of DR (p = 0.003). In conclusion, this is the first report discussing the effect of ARG1 polymorphism on the microvascular complications that are associated with diabetes. Our findings demonstrate that ARG1 rs2781666 SNP is significantly associated with an increased susceptibility to DR in T2DM patients.

LDLR gene polymorphism (rs688) affects susceptibility to cardiovascular disease in end-stage kidney disease patients.

BACKGROUND: The low-density lipoprotein receptor (LDLR) plays a significant role in maintaining the cellular cholesterol homeostasis. Mutations in the LDLR gene can lead to a significant rise in plasma LDL levels that may result in an increased risk of atherosclerosis and coronary heart disease. The purpose of this study was to assess the potential association of the LDLR rs688 polymorphism with cardiovascular disease (CVD) in patients with end-stage kidney disease (ESKD) undergoing hemodialysis. METHODS: In this case-control study the polymorphism was genotyped by the allele specific PCR method in 800 patients with ESKD and 500 healthy controls. The genotype and allele distribution was compared in subgroups of patients with CVD (552) versus those without CVD (248). RESULTS: A significant difference was observed in genotype distribution among ESKD patients and healthy controls. The frequencies of the T allele and TT genotype in ESKD group were significantly higher, with OR (95% CI) 2.2 (1.87-2.6), p <  0.0001 and 5.84 (3.94-8.65), p <  0.0001, respectively. In the he ESKD cohort the distribution of the rs688 was compared between CVD+ and CVD- subgroups. A strong association of the polymorphism with the CVD risk was observed in this analysis. The frequencies of the T allele and TT genotype were significantly higher in CVD+ subgroup, with OR (95% CI) 3.4 (2.71-4.26), p <  0.0001 and 13.2 (7.87-22.09), p <  0.0001, respectively. A multivariate logistic regression analysis was performed to estimate the association between rs688 T variant and risk of CVD. After adjustment for age, sex, BMI, hypertension and diabetes, both CT and TT genotypes were associated with an increased risk of developing CVD in the dominant, recessive and codominant models of inheritance. No significant differences in serum LDL cholesterol levels were found when compared between genotypes. CONCLUSIONS: The present study is the first to demonstrate the association of the LDLR gene polymorphism with increased susceptibility to cardiovascular disease in ESKD patients. This finding needs further investigation to confirm that LDLR rs688 might be a novel genetic risk factor with some prognostic capacity for CVD in ESKD patients.

Renalase gene Glu37Asp polymorphism affects susceptibility to diabetic retinopathy in type 2 diabetes mellitus.

AIMS: Renalase (RNLS) is an enzyme with monoamine oxidase activity that metabolizes circulating catecholamines. The RNLS gene Asp37Glu missense polymorphism (rs2296545) has been associated with hypertension, cardiac hypertrophy and dysfunction, and stroke. The purpose of our study was to investigate the potential involvement of this polymorphism in the microvascular complications of type 2 diabetes (T2DM). METHODS: In this case-control study, the polymorphism was genotyped in 860 patients with T2DM and 400 healthy controls. The genotype and allele distribution was compared in subgroups of patients: with diabetic nephropathy (DN+) (n = 405) versus DN- (independently of the presence of DR) and, similarly, patients with diabetic retinopathy (DR+) (n = 328) versus DR- (independently of the presence of DN). RESULTS: No significant association was detected between analyzed polymorphism and DN. In contrast, the retinopathy subgroup showed a significantly higher frequency of G allele (OR 1.4, 95% CI 1.16-1.72, p = 0.0005) and GG genotype (OR 1.86, 95% CI 1.26-2.75, p = 0.001) than DR- patients. The effect of RNLS Glu37Asp polymorphism on DR remained significant after adjustments for age, gender, BMI, and duration of T2DM (p = 0.005). CONCLUSIONS: This is the first study to investigate RNLS gene polymorphism in microvascular complications of T2DM. The results suggest that RNLS rs2296545 SNP might be considered a risk factor for diabetic retinopathy in T2DM patients. This can provide new insight into the role of renalase gene in the pathophysiology of microvascular complications of diabetes.

Association between p22PHOX gene C242T polymorphism and hypertension in end-stage kidney disease patients.

Oxidative stress plays an important role in hypertension associated vascular damage. It is mediated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation. The C242T polymorphism in the p22PHOX gene encoding essential subunit of NADPH oxidase was associated with CVD, hypertension, and endothelial function. The aim of this study was to assess a potential association of C242T polymorphism with hypertension in end-stage kidney disease (ESKD) patients. DNA samples from 495 patients were genotyped by polymerase chain reaction (PCR) with subsequent cleavage with Rsa I restriction endonuclease. There were no significant differences in genotype and allele distribution between ESKD patients and healthy controls. When patients were stratified into male and female subgroups, there were no differences in the frequency of the T allele (0.35 and 0.34, respectively). Genotype and allele frequencies were also comparable between HY+ and HY- subgroups. We analyzed whether there were any differences between genders in the effect of C242T polymorphism on the presence of hypertension by comparing HY+ males with normotensive males and HY+ females with normotensive females. No difference in polymorphism distribution was found in female subgroup. The significant differences were observed in males. In HY+ subgroup, the frequencies of T allele and TT genotype were higher than in HY- males, with OR 1.91 (1.31-2.8), p = 0.0008 and OR 4.2 (1.67-10.6), p = 0.002, respectively. In conclusion, this is the first study to demonstrate significant association of the p22PHOX gene polymorphism with hypertension in male ESKD patients, with T allele as a risk factor for hypertension.

Association between Monocyte Chemoattractant Protein-1 -2518 (A/G) Single Nucleotide Polymorphism and Chronic Periodontitis in End-stage Renal Disease Patients - A Case-control Study.

Monocyte chemoattractant protein 1 (MCP-1) plays an important role in the development of periodontitis. The purpose of this investigation was to evaluate association of the  MCP-1 gene polymorphism with chronic periodontitis in patients with end-stage renal disease (ESRD). One hundred fifty ESRD patients with chronic periodontitis (CP), 100 without CP and 190 healthy controls were included in this study. Genomic DNA from all participants was genotyped for the -2518 (A/G) polymorphism by a polymerase chain reaction - restriction fragment length polymorphism (PCR--RFLP) assay. Significant differences were observed in the genotype and allele frequencies between patients with ESRD and CP and controls.  The G allele frequency was significantly higher in patients than in control subjects, with odds ratio 1.77 (95 % CI 1.2-2.5), p = 0.0014. For the GG genotype the OR was 3.63 (95 % CI 1.5-8.76), p = 0.041.  No significant differences in the polymorphism distribution were observed between ESRD patients  without CP and control subjects. Comparison of the MCP-1 gene polymorphism distribution in ESRD patients with various primary diseases leading to ESRD did not show any significant differences. The mean MCP-1 serum levels were compared between subgroups. They were significantly higher in ESRD patients with CP (582 ± 112 pg/ml) than in patients without CP (309 ± 103 pg/ml) and controls (265 ± 85 pg/ml). Our results suggest that the MCP-1-2518 A/G  polymorphism might be a novel risk factor for developing chronic periodontitis in patients with ESRD.

Interleukin-1ß Gene (IL1B) Polymorphism and Risk of Developing Diabetic Nephropathy.

Objective: Cytokines play an important role in the pathogenesis of type 2 diabetes (T2DM) and its complications. The aim of the study was to evaluate an association of the -511 (C/T) polymorphism in the IL1B gene with diabetic nephropathy (DN). Methods: The study population included 860 patients with T2DM (506 with diabetic nephropathy and 354 without nephropathy) as well as 505 healthy individuals. Genomic DNA was genotyped for the IL1B -511 (C/T) polymorphism using PCR-RFLP technique. Results: The IL1B -511 C/T polymorphism was genotyped in 860 T2DM patients with or without DN and 505 healthy individuals. The average age of patients was 65.3 years in DN+ and 62.2 years in DN- subgroups. The genotype distribution did not differ significantly between patients and controls. Only a tendency to a slight increase of T allele frequency was observed in patient group. Genotype and allele frequencies of -511 C/T polymorphism were compared in patients with DN and those without it. The minor allele (T) and homozygote TT frequencies were significantly different between subgroups. The T allele was more frequent in DN+ patients, with odds ratio 1.45 (95% CI 1.2-1.8), p = 0.0003. The TT genotype frequency was also higher in DN+, with OR 1.76 (96% CI 1.1-2.7), p = 0.01. Conclusion: In a studied population the -511 C/T polymorphism in the IL1B gene is associated with diabetic nephropathy in dialyzed T2DM patients. Further studies are required to confirm the clinical significance of this finding.

IL4 gene VNTR polymorphism in chronic periodontitis in end-stage renal disease patients.

OBJECTIVE: Interleukin-4 gene polymorphisms were found to be associated with periodontitis. The purpose of this case-control study was to evaluate association of IL4 VNTR polymorphism with periodontitis in patients with end-stage renal disease (ESRD). SUBJECTS AND METHODS: We examined 180 ESRD patients with chronic periodontitis, 82 without CP and 180 healthy controls. Genomic DNA from all subjects was genotyped for the IL4 VNTR polymorphism by polymerase chain reaction (PCR). RESULTS: Genotype distribution in all groups followed Hardy-Weinberg equilibrium. Significant differences in genotype and allele frequencies were observed between groups. The patient group had higher frequency of P1 allele than controls, with odds ratio for P1 allele 1.6 (95% CI 1.1-2.3) and P1P1 genotype 2.73 (95% CI 1.06-7.5). There were no differences in polymorphism distribution between ESRD patients without CP and controls. Periodontal disease was more severe in older patients (≥50 years). Similarly, patients with T2DM had more severe manifestation of CP than patients without diabetes (p = 0.01 for plaque index, p = 0.004 for bleeding index and p = 0.03 for gingival index). CONCLUSION: Our findings suggest that VNTR polymorphism in IL4 gene might be a risk factor for chronic periodontitis in patients with ESRD.

Cholesteryl Ester Transfer Protein Gene Polymorphism (I405V) and Risk of Ischemic Stroke.

BACKGROUND: Cholesteryl ester transfer protein (CETP) plays a major role in the metabolism of high-density lipoprotein. Polymorphisms in the CEPT gene can affect susceptibility to atherosclerosis and cardiovascular disease. The aim of this study was to evaluate the association of the CETP I405V polymorphism with ischemic stroke. METHODS: Five hundred eighty stroke patients and 505 healthy controls were involved in a study. Genomic DNA from all subjects was genotyped for the I405V polymorphism by polymerase chain reaction and restriction analysis. RESULTS: The comparison of stroke and control groups showed a significant increase of V allele and VV genotype in stroke patients (OR 1.61, 95% CI 1.34-1.93 and 2.83, 95% CI 1.78-4.51, respectively). The distribution of alleles and genotypes was also compared between stroke patients with type 2 diabetes mellitus (T2DM) and patients without it. No statistically significant differences were observed between two subgroups. The OR for V allele was 1.15, 95% CI .91-1.46 and for VV genotype 1.25, 95% CI .73-2.15. In comparison of these subgroups separately with controls, the results were similar to obtained for entire STR group. When the distribution of I405V polymorphism in relation to T2DM was analyzed in subgroups of men (n = 296) and women (n = 284) no statistically significant differences were observed. CONCLUSION: Our results demonstrate that the I405V polymorphism in the CETP gene is strongly associated with ischemic stroke. The presence of T2DM did not affect this association. To our knowledge this is the first such association documented in Caucasian population.

Interleukin-4 Gene Intron 3 VNTR Polymorphism in Type 2 Diabetes Patients with Peripheral Neuropathy.

OBJECTIVE: Diabetic peripheral neuropathy (DPN) is one of late complications of diabetes mellitus. The aim of this study was to evaluate the association between variable number tandem repeat (VNTR) polymorphism in intron 3 of interleukin-4 gene and risk of DPN. METHODS: We examined 926 T2DM patients and 420 healthy controls. In the patient group, 44% had DPN. Genomic DNA was isolated from all subjects and genotyped for the IL-4 VNTR polymorphism by polymerase chain reaction (PCR). RESULTS: No significant difference was observed in the frequency of minor P1 allele between T2DM patients and controls (OR 1.00, 95% CI 0.81-1.23, p = 0.988). The distribution of IL-4 VNTR polymorphism was compared between patients with DPN and those without it. The polymorphism was not significantly associated with DPN in studied subjects. In comparison of 406 T2DM patients with DPN and 520 patients without it, the OR (95% CI) for P1 allele was 0.82 (0.65-1.04), p = 0.10 and for P1P1 genotype 1.00 (0.53-1.89), p = 0.991. When two subgroups of patients with DPN, those with cardiovascular disease (CVD) and without CVD, were compared, subgroup with coexisting CVD had significantly higher frequency of P1 allele than patients without CVD, with odds ratio for the P1 allele 3.27 (95% CI 1.83-5.83), p = 0.0001. CONCLUSION: Our results demonstrated that VNTR polymorphism in the IL-4 gene is associated with DPN in type 2 diabetes patients with coexisting CVD.

Pro198Leu Polymorphism in the Glutathione Peroxidase 1 Gene Contributes to Diabetic Peripheral Neuropathy in Type 2 Diabetes Patients.

Glutathione peroxidase 1 (Gpx1) is an endogenous antioxidant enzyme. The T allele of the Pro198Leu polymorphism in the Gpx1 (rs1050450, 198C > T) gene is associated with reduced enzyme activity. The aim of this study was to evaluate the association between Pro198Leu polymorphism and risk of diabetic peripheral neuropathy (DPN). We examined 1244 T2DM patients and 730 healthy controls. In the patient group, 33 % had diabetic peripheral neuropathy. All subjects were genotyped for the Gpx1 Pro198Leu polymorphism by polymerase chain reaction and restriction analysis. A significant increase in the T allele and TT genotype frequencies was observed in DPN patients compared to those without DPN (OR 1.55, 95 % CI 1.30-1.85 and 1.89, 95 % CI 1.30-2.74, respectively). The association remained significant after correction for age, disease duration, HbA1c and BMI. When distribution of T allele was compared between DPN+ and DPN- subgroups and controls, OR was 1.54 for DPN+ and 1.00 for DPN- patients. In conclusion, our findings suggest that Gpx1 Pro198Leu genotypes are significantly associated with the risk of diabetic peripheral neuropathy in patients with T2DM. The study provides new clinically relevant information regarding genetic determinants of susceptibility to diabetic neuropathy.

Interleukin-18 gene polymorphism and risk of CVD in older patients with type 2 diabetes mellitus.

OBJECTIVE: Interleukin-18 (IL-18), a proinflammatory cytokine, plays a key role in the acute and chronic inflammatory processes. It is associated with risk of developing cardiovascular disease (CVD). The aim of this study was to evaluate association between G(-137)C polymorphism (rs187238) in the IL-18 gene and risk of diabetes and CVD in type 2 diabetes patients. METHODS: We examined 1548 T2DM patients and 590 controls. All subjects were genotyped for the G(-137)C promoter region polymorphism by polymerase chain reaction (PCR-SSP). RESULTS: Genotype distribution of the G(-137)C polymorphism showed no significant difference between T2DM patients and controls (p=0.115). An association with CVD was analyzed in two age groups: ⩾65 and <65years. In patients younger than 65years there was a tendency to association of CC genotype with CAD (OR 1.87, 95% CI 1.0-3, p=0.051). In contrast, in subjects aged 65 or older, the C allele and CC genotype showed the significant association with the presence of CVD, with the OR 1.99, p=0.001 and OR 5.31, p=0.006, respectively. The C allele carriers showed the higher prevalence of CVD compared to non-carriers (61% vs. 39%, p<0.0001). CONCLUSION: Older T2DM patients carrying the C allele of IL-18 G(-137)C polymorphism have a significantly increased risk of CVD.

Association between functional variant of inflammatory system gene (PSMA6) and end-stage kidney disease.

BACKGROUND: The proteasome system is involved in several disorders. The 5' untranslated region of PSMA6 gene contains a single nucleotide polymorphism (SNP) -8 C/G, associated with diabetes, myocardial infarction and coronary artery disease. METHODS: We examined 584 patients with end-stage kidney disease (ESKD) and 430 controls. All were genotyped for -8 C/G SNP by polymerase chain reaction and restriction analysis. RESULTS: We observed lower frequency of CG + GG genotypes in patients than in controls (20 vs. 42 %, p = 0.0038). The odds ratio of 0.34 (95 % CI 0.26-0.45) suggests association of CG + GG with decreased risk of ESKD. We investigated the association between PSMA6 polymorphism and LVH present in 54 % of patients. There was a significant association of CG + GG genotype with LVH, with over 75 % of CG + GG in patients with LVH. This effect was independent from other common causes of LVH-age (OR 1.12, p = 0.643) and hypertension (OR 1.72, p = 0.422). CONCLUSION: We demonstrated for the first time that PSMA6 polymorphism might be a protective factor for ESKD. On the other hand, CG + GG genotypes are independently related to LVH in ESKD patients.

The effect of Toll-like receptor 4 gene polymorphism on vascular complications in type 2 diabetes patients.

OBJECTIVE: The aim of our study was to assess the association between the TLR4 Asp299Gly polymorphism and vascular complications in patients with type 2 diabetes. METHODS: We examined 1090 patients with T2DM and 716 healthy controls. All subjects were genotyped for the Asp299Gly polymorphism by polymerase chain reaction (PCR) and restriction analysis. RESULTS: The genotype frequencies of the Asp299Gly polymorphism were similar in T2DM patients and controls (p=0.512 and 0.311, respectively). The polymorphism was analyzed in subgroups of patients with macro- and microvascular complications. The distribution of genotypes was significantly different between patients with CVD and those without CVD. A significant increase of G allele frequency was observed in CVD+ patients, with odds ratio 2.06 (1.27-3.34), p=0.0035. The same effect was found when patients with diabetic retinopathy were compared with those without it (OR for G allele 2.12, 95% CI 1.43-3.12, p=0.0002). There were no statistically significant differences in genotype distribution between patients with diabetic nephropathy or neuropathy and those without these complications. CONCLUSIONS: The results of our study demonstrated that the G allele of the Asp299Gly polymorphism of the TLR4 gene is associated with increased risk of cardiovascular disease and diabetic retinopathy in type 2 diabetes patients.

Rs10887800 renalase gene polymorphism is associated with an increased risk of coronary artery disease in hemodialyzed patients.

PURPOSE: Coronary artery disease (CAD) is common in patients with end-stage renal disease (ESRD). Recent studies have suggested that renalase, a novel FAD-dependent amine oxidase, may play an important role in the pathogenesis of cardiovascular complications in ESRD patients. The aim of the study was to investigate the association between renalase gene polymorphisms and a risk of CAD in patients on hemodialysis. METHODS: In a case-control study, a total of 309 hemodialyzed patients (107 with and 202 without CAD) were genotyped for two SNPs in the renalase gene (rs10887800 and rs2576178) using the PCR-RFLP method. RESULTS: By multivariate logistic regression analysis, we found that rs10887800GG genotype was associated with an increased risk of CAD under the codominant model [GG vs AA; adjusted OR 2.66 (95 % CI, 1.19-5.94), p = .017] and under the recessive model [GG vs AG + AA; adjusted OR 2.10 (95 % CI, 1.10-4.02), p = .025]. The rs2576178 polymorphism did not influence the risk of CAD. CONCLUSION: The study suggested for the first time that the rs10887800 renalase gene polymorphism may be involved in the pathogenesis of CAD in hemodialyzed patients and thus could be considered a new genetic risk factor for CAD in this population.

Effect of G(-174)C polymorphism in interleukin-6 gene on cardiovascular disease in type 2 diabetes patients.

Interleukin-6 (IL-6) is an important pro-inflammatory cytokine of relevance to cardiovascular diseases. The aim of this case-control study was to evaluate the association between the G(-174)C functional polymorphism in the IL-6 gene and risk of cardiovascular disease (CVD) in type 2 diabetes patients. We examined 1090 patients with T2DM and 612 controls. All subjects were genotyped for the G(-174)C polymorphism by polymerase chain reaction (PCR) and restriction analysis. There were no significant differences in the distribution of genotypes and alleles between T2DM patients and healthy controls. Significantly higher C allele frequency was observed in CVD+ patients compared to CVD- subgroup (53% vs. 32%, p<0.0001). The odds ratio for C allele was 2.4 (95% CI 1.99-2.9, p<0.0001) and for CC genotype 4.55 (95% CI 3.12-6.63, p<0.000). When the distribution of G(-174)C polymorphism was compared in subgroups with different clinical phenotypes of CVD, a significant association of CC genotype with myocardial infarction was observed. Forty eight percent of patients with MI had the CC genotype compared to 22% of patients without MI (p<0.0001). In conclusion, type 2 diabetes patients carrying the C allele of the IL-6 G(-174)C polymorphism have a significantly increased risk of CVD.

Receptor for advanced glycation end products (RAGE) gene polymorphism and cardiovascular disease in end-stage renal disease patients.

BACKGROUND/OBJECTIVES: Receptor for advanced glycation end products (RAGE) contributes to the pathogenesis of vascular and inflammatory diseases. We investigated whether the functional polymorphism in the promoter region of the RAGE gene (-374 T/A) influences development of cardiovascular disease in the end-stage renal disease (ESRD) patients. METHODS: The cohorts of 1866 ESRD patients and 1143 healthy subjects were genotyped by polymerase chain reaction (PCR) for the RAGE variant rs1800624. RESULTS: The genotype and allele frequencies did not differ significantly between ESRD patients and controls. There was no significant difference in the genotype distribution when patients with CVD were compared to those without it (p for A allele = 0.62). After stratifying CVD patients according to CVD clinical phenotype, the ESRD patients with stroke had a lower frequency of A allele than patients without CVD (0.12 vs. 0.21, p = 0.027). To confirm this finding, we genotyped 163 patients with ischemic stroke but without renal disease. In this group, the AA/TA genotypes were also significantly associated with lower risk of stroke (OR 0.46, p = 0.0002). CONCLUSION: Our data suggest that the presence of the A allele of -374 T/A polymorphism in the RAGE gene has a protective effect against stroke.

Matrix Metalloproteinase-9 (MMP-9) Gene Polymorphism in Stroke Patients.

Matrix metalloproteinases (MMPs), endopeptidases degrading extracellular matrix, play an important role in the pathogenesis of atherosclerosis and vascular disease. The aim of this study was to evaluate the association between the C(-1562)T functional polymorphism in the MMP-9 gene and risk of stroke. We examined 322 patients with stroke and 410 controls. In the patient group, 52 % had type 2 diabetes. All subjects were genotyped for the C(-1562)T polymorphism by polymerase chain reaction and restriction analysis. A significant increase in T allele and CT + TT genotype frequencies was observed in patients compared with controls (OR 1.73, 95 % CI 1.34-2.23 and 1.89, 95 % CI 1.39-2.56, respectively). The T allele carriers were younger at the onset of stroke (63.5 ± 11.7 years) than patients with CC genotype (71 ± 14.1 years) (p = 0.0002). The comparison between patients with T2DM and without it showed that the T allele and CT + TT genotype were more frequent in T2DM patients (OR 1.48, 95 % CI 1.03-2.12 for T allele and 1.44, 95 % CI 1.93-2.24 for CT + TT genotype). In conclusion, our findings suggest that MMP-9 C(-1562)T polymorphism is significantly associated with risk of stroke in patients with and without T2DM.