Renal tubulointerstitium plays an important role in the development and progression of diabetic nephropathy. The aim of this study was to assess serum cystatin C and 2 renal tubular enzymes, neutrophil gelatinase associated lipocalin (NGAL) and N-acetyl-beta-D-glucosaminidase (NAG), as screening markers for early renal dysfunction in patients with type 2 diabetes mellitus (T2DM). ROC curve analysis showed that urinary NAG is the most sensitive marker of microalbuminuria and early renal damage with sensitivity of 83.3%, while serum cystatin C was the most sensitive and specific marker of macroalbuminuria and damage progress with sensitivity of 70.8% and specificity of 83.3% versus 70.6% and 83.3% for uNGAL; and 64.7% and 66.7% for NAG, respectively. Our data indicate that urinary NAG is the most sensitive marker for early renal damage in diabetic patients. However, for damage progress, serum cystatin C is the most sensitive and specific marker for follow-up and monitoring renal dysfunction.
BackgroundLipoprotein-related mechanisms have been associated with damage to the cardiovascular system in diabetic patients. Apolipoprotein E gene which affects the clearance of lipoproteins and consequently the lipid profile in our body is one of the most studied candidate genes and recently has been reported to be associated with T2DM and CAD. In this work, we studied the association of apoE gene polymorphism with T2DM and CVD and its effect on plasma lipids profile.MethodsOur study was conducted on 284 subjects categorized into 100 patients with T2DM, 100 patients with T2DM complicated with CVD and 84 normal control subjects. ApoE gene polymorphism was genotyped by real-time PCR using TaqMan® SNP Genotyping Assay.ResultsApoE E3/E3 genotype was the most common in our subjects. The frequencies of E3/E4 genotype and ε4 allele were increased in both T2DM patients and CVD patients as compared with controls, but were significant only in CVD patients (p = 0.004 and 0.007, respectively). Diabetic patients who carried E3/E4 genotype were at 2.4-fold increased risk to develop CVD (95 % CI 1.14–5.19, P = 0.02) and the ε4 allele associated with 2.23-fold higher CVD risk (95 % CI 1.09–4.59, P = 0.02). After adjustment for other established risk factors, E3/E4 genotype was an independent risk factor for CVD (OR = 2.3, p = 0.009) but not for T2DM (OR = 1.7, p = 0.28), while ε4 allele was an independent risk factor for both T2DM (OR = 2.2, p = 0.04) and CVD (OR = 3.0, p = 0.018) with 5.9-fold increased risk to develop CVD in T2DM patients (p = 0.019). E3/E4 genotype associated with significantly higher levels of TC and non HDL-C in all groups and with significantly higher levels of LDL-C in both T2DM and CVD patients.ConclusionsApoE gene polymorphisms associate with CVD and affect the lipid profile. The ε4 allele is an independent risk factor for both T2DM and CVD. Further genetic studies to add information beyond the traditional cardiovascular risk factors in T2DM and to identify risk genotypes will help in early prediction and identification of at risk patients.
Neopterin has been measured in many autoimmune diseases and was reported as a marker of cellular immunity activation in rheumatoid asthritis (RA). The aim of this work was to assess serum neopterin as a marker of disease activity in treated RA patients. We measured serum level of neopterin in 120 treated RA patients and 100 age- and sex-matched controls by high-performance liquid chromatography (HPLC) method, and disease activity score was calculated in all patients by DAS28-CRP score. Significantly higher levels of neopterin were observed in RA patients (11.46 ± 3.56 nmol/L) compared to healthy controls (4.74 ± 1.98 nmol/L), P < 0.0001. Significantly higher neopterin levels were observed among male RA patients [median (IQR), 13.44 (12.65-16.21)] than female RA patients [median (IQR), 11.86 (7.91-13.44)], P <0.0001. No significant correlations between neopterin and age, age of disease onset, disease duration, or any of the disease activity parameters were found. Moreover, no significant difference regarding neopterin levels in different disease activity phases was identified. Our results indicated that neopterin is a marker of RA but not a marker of disease activity in treated RA patients.
In this work we studied association of common variants in transcription factor 7-like 2 (TCF7L2) and cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1) genes with type 2 diabetes mellitus (T2DM) in Egyptians.Subjects and methodsThis is a case–control study; 180 T2DM patients and 210 control subjects were genotyped for TCF7L2 rs7903146 and rs12255372 and CDKAL1 rs7756992 single nucleotide polymorphisms (SNPs) by TaqMan method on real time polymerase chain reaction system (real time-PCR).ResultsTCF7L2 rs12255372 and rs7903146 associated with T2DM (p = 0.0001 and 0.003; respectively). The rs12255372 variant T allele associated with 2-fold increased risk for T2DM and TT genotype carriers were at 3.58-folds higher risk to develop T2DM than wild genotype (GG) carriers. Meanwhile, rs7903146 variant T allele associated with 1.6-fold increased risk for T2DM and TT genotype carriers were at 2.3-folds higher risk than wild genotype (CC) carriers. Both TCF7L2 SNPs significantly associated with T2DM under additive and dominant models and after adjustment for other covariates. On the other hand, CDKAL1 rs7756992 showed no significant association with T2DM under any genetic model. Both TCF7L2 SNPs were in strong LD (P = 0.02; D′ = 0.85). Taking common TCF7L2 rs12255372/rs7903146 GC haplotype as reference, multivariate analysis confirmed the association of rs12255372 T allele-containing haplotypes (TC and TT) with T2DM. Haplotype TC associated with 6.32 times-higher risk for T2DM (95%CI = 0.55–76.17, Pc = 0.04) followed by haplotype TT which associated with 3.88 times-higher risk for the disease (95%CI = 1.09–13.76, Pc = 0.03).ConclusionTCF7L2 rs12255372 and rs7903146 common variants associate with T2DM risk in Egyptians.
The aim of this study was to investigate association of protein tyrosine phosphatase non-receptor type 22 (PTPN22) rs2476601 and signal transducer and activator of transcription 4 (STAT4) rs7574865 polymorphisms with rheumatoid arthritis (RA) susceptibility and to assess potential association with the status of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies, serum neopterin, and disease activity. RF, anti-CCP antibodies, and neopterin were assayed in serum of 100 unrelated RA patients and 114 controls. STAT4 rs7574865 G/T and PTPN22 rs2476601 C/T polymorphisms were genotyped by the TaqMan allelic discrimination method. The frequency of STAT4 variant allele was significantly higher in RA patients than in controls (p = 0.01), while the variant allele of PTPN22 was identified in only two RA patients, in a heterozygous form and in none of control subjects. The frequency of STAT4 variant allele carrier genotypes (GT+TT) was significantly higher among RA patients than in controls (43.7 vs. 10.5%, p = 0.02) and associated with RA under additive and dominant models. The frequency of RF and anti-CCP positivity was significantly higher among RA patients carrying T allele genotypes compared to patients carrying wild genotype (P = 0.02 and 0.04, respectively). No significant associations between STAT4 variant and serum neopterin or disease activity parameters were identified. Our study confirmed the association of STAT4 rs7574865 polymorphism with RA and was the first to indicate an association with RF and anti-CCP antibodies positivity. We also found PTPN22 rs2476601 has no role in susceptibility to RA in Egyptian patients.
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