Relationship between cytotoxic T-lymphocyte antigen 4 -318C/T (rs5742909) gene polymorphism and the risk of acute rejection in renal transplantation.

Results on the relationship between CTLA4 -318C/T (rs5742909) gene polymorphism and risk of acute rejection in renal transplantation are still conflicting. This meta-analysis was performed to update the association between CTLA4 -318C/T and risk of acute rejection in renal transplantation. The association investigations were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using meta-analysis method. Twelve reports were included in this meta-analysis for the association of CTLA4 -318C/T gene polymorphism with acute rejection risk in renal transplantation, consisting of 728 acute rejection patients and 1628 non-acute rejection controls. The association between CTLA4 -318C/T gene polymorphism and acute rejection risk in renal transplantation for overall populations was not found in this meta-analysis (T allele: OR=0.96, 95% CI: 0.60-1.54, P=.88; TT genotype: OR=0.90, 95% CI: 0.47-1.71, P=.74; CC genotype: OR=1.00, 95% CI: 0.62-1.59, P=.98). Interestingly, T allele was associated with the risk of acute rejection in renal transplantation in African population. In conclusion, CTLA4 -318C/T gene polymorphism is not associated with the risk of acute rejection in renal transplantation in overall populations.

Potential signal pathway between all-trans retinoic acid and LMX1B in hypoxia-induced renal tubular epithelial cell injury.

All-trans retinoic acid (ATRA), an active metabolite of vitamin A, exerts various effects on physiological processes such as cell growth, differentiation, apoptosis and inflammation. LMX1B, a developmental LIM-homeodomain transcription factor, is widely expressed in vertebrate embryos, and it takes part in the development of diverse structures such as limbs, kidneys, eyes, brains, etc. Renal tubular epithelial cell culture was performed, and mRNA and protein expression of some factors were detected. We recently demonstrated that ATRA up-regulated the LMX1B, and down-regulated the transforming growth factor-ß1, collagen IV and fibronectin in a hypoxia/reoxygenation (H-R) injury system in renal tubular epithelial cells (RTEC). In conclusion, ATRA acts as a positive regulator of LMX1B in H-R RTEC.

Signaling pathway factors expression in renal tissue of apoE-knockout mice.

Apolipoprotein E (apoE) is regarded as one of the major plasma lipoproteins, and it plays an important role in the transport and metabolism of lipids. apoE can be found in multiple tissues, such as liver, kidney, jejunum, urinary bladder, ileum, colon, brain, adrenal glands, lung, ovary, spleen, pancreas, and testis, etc. As a secreted protein, it plays an important role in the systemic lipoprotein metabolism and vascular wall homeostasis and in the pathogenesis of renal diseases. apoE-knockout (apoE(-/-)) mice is a classic model of atherosclerosis and renal diseases. However, no review summed up the signaling pathway factors expression in renal tissue of apoE-knockout mice. The literatures were searched extensively and this review was performed to review the signaling pathway factors expression in renal tissue of apoE-knockout mice.

Association between plasminogen activator inhibitor-1 4G/5G gene polymorphism and immunoglobulin A nephropathy susceptibility.

The association between plasminogen activator inhibitor-1 (PAI-1) 4 G/5 G gene polymorphism and immunoglobulin A nephropathy (IgAN) risk is still controversial. A meta-analysis was performed to evaluate the association between PAI-1 4 G/5 G gene polymorphism and IgAN susceptibility. A predefined literature search and selection of eligible relevant studies were performed to collect data from electronic database. Four articles were identified for the analysis of association between PAI-1 4 G/5 G gene polymorphism and IgAN risk. 4 G allele was not associated with IgAN susceptibility in overall populations and in Asians. Furthermore, 4 G/4 G and 5 G/5 G genotype were not associated with IgAN for overall populations, Asians. In conclusion, PAI-1 4 G/5 G gene polymorphism was not associated with IgAN risk in overall populations and in Asians. However, more studies should be performed in the future.

Association of vitamin D receptor BsmI (rs1544410) gene polymorphism with the chronic kidney disease susceptibility.

Association of vitamin D receptor (VDR) BsmI (rs1544410) gene polymorphism with the chronic kidney disease (CKD) susceptibility from the published reports are still conflicting. This meta-analysis was performed to evaluate the relationship between VDR BsmI (rs1544410) gene polymorphism and the risk of CKD. The association studies were identified from PubMed, Cochrane Library and China Biological Medicine Database on 1 March 2014, and eligible investigations were included and synthesized using meta-analysis method. Nine reports were recruited into this meta-analysis for the association of VDR BsmI gene polymorphism with CKD susceptibility. In this meta-analysis for overall populations, the BsmI B allele BB genotype and bb genotype were not associated with the risk of CKD (B allele: OR = 1.12, 95% CI: 0.88-1.44, p = 0.36; BB genotype: OR = 1.15, 95% CI: 0.81-1.62, p = 0.43; bb genotype: OR = 0.86, 95% CI: 0.61-1.20, p = 0.36). Furthermore, VDR BsmI gene polymorphism was not associated with CKD susceptibility in Asians and in Caucasians. In conclusion, the BsmI gene polymorphism was not associated with CKD susceptibility in overall populations, in Asians and in Caucasians. However, more studies should be conducted to confirm it.

Roles of miR-497 and its potential signaling pathway in diseases and with vascular endothelial growth factor.

MicroRNA (miRNA) is a class of small endogenous non-coding RNAs that are ∼ 22 nucleotides in length and can have structural, enzymatic and post-transcriptional regulators of gene expression targeting mRNA for translational repression and/or degradation. miR-497 is high on the list of noncoding, small, regulatory RNAs that plays important roles in the pathogenesis of some diseases and takes part in some signaling pathways in some diseases, but many questions await answers. Vascular endothelial growth factor (VEGF) is a notable chemokine that plays critical roles in angiogenesis and vasculogenesis. There might be an association between miRNA-497 and VEGF. This review was performed to sum up the roles of miR-497 and its potential signaling pathway in diseases and with VEGF.

Association of vitamin D receptor gene polymorphism with the risk of systemic lupus erythematosus.

Relationship between vitamin D receptor (VDR) gene polymorphism and the risk of systemic lupus erythematosus (SLE) from the published reports are still conflicting. This study was conducted to evaluate the relationship between VDR BsmI (rs1544410), Fok1 (rs2228570), ApaI (rs7975232) and TaqI (rs731236) gene polymorphism and the risk of SLE using meta-analysis method. The association studies were identified from PubMed and Cochrane Library on 1 March 2014, and eligible investigations were included and synthesized using meta-analysis method. Thirteen reports were recruited into this meta-analysis for the association of VDR gene polymorphism with SLE susceptibility. In this meta-analysis for overall populations, the BsmI B allele and bb genotype, Fok1 f allele and ff genotype, and ApaI aa genotype, were associated with the risk of SLE. In Asians, the BsmI B allele, BB genotype and bb genotype, Fok1 f allele and ff genotype were associated with the risk of SLE. In Africans, the BsmI B allele, BB genotype and bb genotype, Fok1 f allele and ff genotype, ApaI A allele, AA genotype and aa genotype were associated with the risk of SLE. However, VDR BsmI, Fok1, ApaI and TaqI gene polymorphism were not associated with the risk of SLE in Caucasians. In conclusion, the BsmI B allele and bb genotype, Fok1 f allele and ff genotype were associated with the risk of SLE in overall populations, and in Asians, but these associations were not found in Caucasians. However, more studies should be conducted to confirm it.

Association of vitamin D receptor Fok1 (rs2228570), TaqI (rs731236) and ApaI (rs7975232) gene polymorphism with the risk of chronic kidney disease.

Relationship between vitamin D receptor (VDR) gene polymorphism and the risk of chronic kidney disease (CKD) from the published reports are still conflicting. This study was conducted to evaluate the relationship between VDR Fok1 (rs2228570), TaqI (rs731236) and ApaI (rs7975232) gene polymorphism and the risk of CKD using meta-analysis method. The association studies were identified from PubMed and Cochrane Library on 1 March 2014, and eligible investigations were included and synthesized using meta-analysis method. Five reports were recruited into this meta-analysis for the association of VDR Fok1, TaqI and ApaI gene polymorphism with CKD susceptibility. In this meta-analysis, VDR Fok1, TaqI and ApaI gene polymorphism were not associated with CKD susceptibility for overall populations and in Caucasians. However, the Fok1 f allele, ff genotype and FF genotype were associated with the risk of CKD in Asians. In conclusion, VDR Fok1, TaqI and ApaI gene polymorphism were not associated with CKD risk in overall populations and in Caucasians. But, the Fok1 gene polymorphism was associated with the risk of CKD in Asians. However, more studies should be conducted to confirm it.

Association of vitamin D receptor gene polymorphism with the urine calcium level in nephrolithiasis patients.

Association of vitamin D receptor (VDR) gene polymorphism with the urine calcium level in nephrolithiasis patients from the published reports are still conflicting. This study was conducted to evaluate the relationship between VDR BsmI (rs1544410), Fok1 (rs2228570), TaqI (rs731236) and ApaI (rs7975232) gene polymorphism and urine calcium level in nephrolithiasis patients using meta-analysis method. The association studies were identified from PubMed, and Cochrane Library on 1 April 2014, and eligible investigations were included and synthesized using meta-analysis method. Four reports were recruited into this meta-analysis for the association of VDR BsmI, Fok1, TaqI and ApaI gene polymorphism with urine calcium level in nephrolithiasis patients. In this meta-analysis, VDR BsmI B allele and BB genotype, Fok1 f allele and ff genotype, TaqI, and ApaI gene polymorphism were not associated with urine calcium level in nephrolithiasis patients. However, the BsmI bb genotype and Fok1 FF genotype were associated with the urine calcium level in nephrolithiasis patients. In conclusion, VDR BsmI bb genotype and Fok1 FF genotype were associated with the urine calcium level in nephrolithiasis patients. However, more studies should be conducted to confirm it.

Association of vitamin D receptor BsmI (rs1544410) gene polymorphism with the intact parathyroid hormone (iPTH) level among patients with end-stage renal disease.

Association of vitamin D receptor (VDR) BsmI (rs1544410) gene polymorphism with the intact parathyroid hormone (iPTH) level among patients with end-stage renal disease (ESRD) from the published reports is still conflicting. This meta-analysis was performed to evaluate the relationship between VDR BsmI (rs1544410) gene polymorphism and the iPTH level among patients with ESRD. The association studies were identified from PubMed, and Cochrane Library on 1 March 2014, and eligible investigations were included and synthesized using meta-analysis method. Six reports were recruited into this meta-analysis for the association of VDR BsmI gene polymorphism with iPTH level among patients with ESRD. In this meta-analysis, the iPTH level in ESRD patients carrying BsmI Bb genotype was higher than that in ESRD patients carrying bb genotype in overall populations (Bb versus bb: OR = 61.40, 95% CI: 19.65-103.16, p = 0.004). However, the iPTH level in ESRD patients carrying BB genotype was not significant different from that in ESRD patients with Bb genotype and bb genotype in overall populations (BB versus Bb: OR = -18.30, 95% CI: -126.28-89.69, p = 0.74; BB versus bb: OR = 22.85, 95% CI: -70.81-116.51, p = 0.63). Furthermore, the results for Caucasians were similar to those in overall populations. In conclusion, the iPTH level in ESRD patients carrying BsmI Bb genotype was higher than that in ESRD patients carrying bb genotype in overall populations and in Caucasians. However, more studies should be conducted to confirm it.

Relationship between MCP-1 promoter -2518 A/G gene polymorphism (rs1024611) and systemic lupus erythematosus/lupus nephritis.

Results from the published studies on the association between monocyte chemoattractant protein-1 (MCP-1) promoter -2518 A/G (rs1024611) gene polymorphism and systemic lupus erythematosus (SLE)/lupus nephritis (LN) are still conflicting. This meta-analysis was performed to evaluate the relationship between MCP-1 A/G gene polymorphism and SLE/LN and to explore whether MCP-1 A allele, AA genotype or GG genotype could become a predictive marker for SLE/LN risk. Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) as of 1 January 2014, and eligible investigations were synthesized using meta-analysis method. Results were expressed with odds ratios (OR) for dichotomous data, and 95% confidence intervals (CI) were also calculated. Sixteen investigations were identified for the analysis of association between MCP-1 A/G gene polymorphism and SLE, consisting of 2425 patients with SLE and 2567 controls. In the overall populations, Asians, Caucasian population, the association between MCP-1 A/G gene polymorphism and SLE susceptibility was not found. Interestingly, a trend toward an association between A allele/AA genotype and LN risk was observed in overall populations, although there was no statistical difference. However, this meta-analysis indicated that AA genotype was associated with LN risk in Caucasians (OR = 0.71; 95% CI: 0.54-0.93; p = 0.01). In conclusion, our results indicate that AA homozygous might be a significant genetic molecular marker to predict the SLE patients developing into LN in Caucasians. However, more investigations are required to further clarify this association.

Association of vitamin D receptor BsmI (rs1544410), Fok1 (rs2228570), TaqI (rs731236) and ApaI (rs7975232) gene polymorphism with the nephrolithiasis susceptibility.

Association of vitamin D receptor (VDR) gene polymorphism with the risk of nephrolithiasis from the published reports is still conflicting. This study was conducted to evaluate the relationship between VDR BsmI (rs1544410), Fok1 (rs2228570), TaqI (rs731236) and ApaI (rs7975232) gene polymorphism and the risk of nephrolithiasis using meta-analysis method. The association studies were identified from PubMed, and Cochrane Library on 1 April 2014, and eligible investigations were included and synthesized using meta-analysis method. Six reports were recruited into this meta-analysis for the association of VDR BsmI, Fok1, TaqI and ApaI gene polymorphism with nephrolithiasis susceptibility. In this meta-analysis, VDR BsmI, Fok1, TaqI and ApaI gene polymorphism were not associated with nephrolithiasis susceptibility for overall populations and in Caucasians. However, the Fok1 f allele and ff genotype were associated with the risk of nephrolithiasis in Asians, but the FF genotype not. Furthermore, TaqI TT genotype was associated with the risk of nephrolithiasis in Asians, but the t allele and tt genotype not. However, ApaI gene polymorphism was not associated with nephrolithiasis susceptibility in Asians. In conclusion, VDR BsmI, Fok1, TaqI and ApaI gene polymorphism were not associated with nephrolithiasis risk in overall populations and in Caucasians. But, the Fok1 f allele and ff genotype, TaqI TT genotype, ApaI gene polymorphism were associated with the risk of nephrolithiasis in Asians. However, more studies should be conducted to confirm it.

Association of Megsin gene polymorphism with IgA nephropathy risk.

This meta-analysis was conducted to assess the association of Megsin 2093C/T, 2180C/T, C25663G gene polymorphism with the risk of IgA nephropathy (IgAN). The association literatures were identified from PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) on 1 January 2014, and eligible reports were recruited and synthesized. Seven eligible reports were recruited into this meta-analysis for the association of Megsin 2093C/T, 2180C/T, C25663G gene polymorphism with IgAN risk. In this meta-analysis, the association of Megsin 2093C/T TT genotype with IgAN risk in Asians was found. Interestingly, Megsin C25663G G allele and GG genotype were associated with the risk of IgAN in Asian population. However, Megsin 2180C/T gene polymorphism was not associated with IgAN risk in Asians. In conclusion, Megsin 2093C/T TT genotype, and C25663G G allele and GG genotype were associated with the risk of IgAN in Asian population. However, more studies should be performed in the future to confirm this association.

Association of monocyte chemoattractant protein-1 2518G/A gene polymorphism with diabetic nephropathy risk.

Results from the published studies on the association between monocyte chemoattractant protein-1 (MCP-1) -2518 A/G gene polymorphism and diabetic nephropathy (DN) risk are still conflicting. This meta-analysis was performed to evaluate the relationship between MCP-1 A/G gene polymorphism and DN risk and to explore whether MCP-1 A allele, AA genotype or GG genotype could become a predictive marker for DN risk. Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) as of 1 March 2014, and eligible investigations were synthesized using meta-analysis method. Four studies were identified for the analysis of association between MCP-1 A/G gene polymorphism and DN risk, and all the included studies were form Asian population. The association between MCP-1 A/G gene polymorphism and DN susceptibility was not found (A allele: OR = 1.19; 95% CI: 0.97-1.45; p = 0.10; AA genotype: OR = 1.27; 95% CI: 0.95-1.70; p = 0.11; GG genotype: OR = 0.77; 95% CI: 0.57-1.05; p = 0.10). In the sensitive analysis, according to the control source from hospital, we found that AA genotype was associated with the DN risk (OR = 1.45; 95% CI: 1.05-2.00; p = 0.02). However, other associations were not found in the sensitive analysis according to the control source from hospital or population. Our results indicate that AA homozygous might be a significant genetic molecular marker to predict the diabetes mellitus patients developing into DN. However, more investigations are required to further clarify this association.

Role of MAPK signal pathways in differentiation process of M2 macrophages induced by high-ambient glucose and TGF-ß1.

Macrophage can be alternatively activated by TGF-ß1, whether high-ambient glucose can enhance the sensitivity of TGF-ß1 and the intracellular mechanisms involved in this process are not fully understood. We examined whether the mitogen-activated protein kinase is involved in the activation of macrophage induced by TGF-ß1 and high-ambient glucose. The expression of arginase-1, CD206 and TGF-ß1 was accessed by Western blot and immunofluorescence in RAW 264.7 cells stimulated with TGF-ß1 and high-ambient glucose. The activation of MAPK pathways in the process was investigated by Western blot. The role of MAPK was assessed using biochemical inhibitors. The protein of arginase-1, CD206 and TGF-ß1 was significantly overexpressed in RAW264.7 cells stimulated by TGF-ß1 and high-ambient glucose. ERK and JNK phosphorylation occurred in 30 min and p38MAPK phosphorylation occurred in 30 min and 24 h after the stimulation. And the expression of arginase-1 and TGF-ß1 was partially blocked by the pretreated ERK biochemical inhibitor (U0126) instead of the JNK inhibitor (SP600125) and p38MAPK inhibitor (SB203580). In conclusion, high-ambient glucose can enhance the sensitivity of TGF-ß1 in RAW264.7 cells, which resulted in overexpression of TGF-ß1 and arginase-1 in macrophages. ERK plays a role in this process.

The potential signaling pathway between peroxisome proliferator-activated receptor gamma and retinoic acid receptor alpha in renal interstitial fibrosis disease.

Peroxisome proliferator-activated receptorγ (PPARγ) can regulate the process of cell apoptosis and is related to the progression of renal disorders. Retinoic acid receptor alpha (RARα) is one of the nuclear receptors involved in a variety of kidney diseases. Renal interstitial fibrosis (RIF) is a common denominator of chronic kidney disease (CKD). This study investigated whether a potential signaling pathway existed between PPARγ and RARα in RIF rats with unilateral ureteral obstruction (UUO). The rats were randomly divided into four groups: a model group subjected to UUO (GU), and three other groups treated with rosiglitazone sodium (GRS), GW9662 and dimethyl sulfoxide (DMSO), n = 40, respectively. Renal tissues were collected two and four weeks after post-surgery. The relevant indicators were detected. In comparison with the GU group, the expressions of PPARγ and RARα (protein and mRNA) were increased in the GRS group, and decreased in the GW9662 group (all p < 0.01). The RIF index, mRNA and protein expression of transforming growth factor-ß1 (TGF-ß1), and the protein expressions of collagen-IV (Col-IV) and fibronectin (FN) in the GRS group were more markedly reduced than those in the GU group; their levels in the GW9662 group were elevated (all p < 0.01). PPARγ or RARα was negatively correlated to the RIF index, TGF-ß1, Col-IV and FN. PPARγ was positively correlated with RARα (all p < 0.01). In conclusion, PPARγ agonist can elevate the expression of PPARγ or RARα in RIF rats. There might be a potential signaling pathway between PPARγ and RARα in RIF disease.

Is there an association of hepatitis B virus infection with minimal change disease of nephrotic syndrome? A clinical observational report.

The rate of hepatitis B virus (HBV) infection is high in the Chinese population, and the implications of HBV infection are widely recognized, and membranous nephropathy is the most common renal lesion to be associated with HBV infection. Minimal change disease (MCD) is one of the most important histopathological characteristics in patients with nephrotic syndrome. There is no any study to report that HBV infection is associated with the etiology of MCD. Herein, we report four MCD patients with HBV infection and speculate that there is an association of HBV infection with the pathological type of MCD. In this study, we also reported the treatment schedule for these four MCD patients, and found that the anti-virus alone and combination of anti-virus with immunosuppressive agent could obtain a benefit for MCD patients with HBV infection. However, a well-designed study should be performed to confirm this association.

Association of endothelial nitric oxide synthase gene polymorphism with the risk of Henoch-Schönlein purpura/Henoch-Schönlein purpura nephritis.

Association between endothelial nitric oxide synthase (eNOS) gene polymorphism and Henoch-Schönlein purpura (HSP)/Henoch-Schönlein purpura nephritis (HSPN) risk is still controversial. A meta-analysis was performed to evaluate the association between eNOS gene polymorphism and HSP/HSPN susceptibility. A predefined literature search and selection of eligible relevant studies were performed to collect data from electronic database. Three articles were identified for the analysis of association between eNOS gene polymorphism and HSPN/HSP risk. eNOS G894T gene polymorphism was not associated with HSPN susceptibility and the risk of patients with HSP developing into HSPN. Interestingly, eNOS G894T T allele and GG genotype were associated with HSP susceptibility, but not the TT genotype. eNOS T786C TT genotype was associated with HSPN susceptibility, but not C allele and CC genotype. Furthermore, eNOS T786C gene polymorphism was not associated with HSP risk and the risk of patients with HSP developing into HSPN. In conclusion, eNOS T786C TT genotype was associated with and eNOS G894T T allele and GG genotype were associated with HSP susceptibility. However, more studies should be performed in the future.

Association of angiotensin II type-1 receptor A1166C gene polymorphism with the susceptibility of immunoglobulin A nephropathy.

Association of angiotensin II type-1 receptor (AT1R) A1166C gene polymorphism with the susceptibility of immunoglobulin A nephropathy (IgAN) is still controversial. This meta-analysis was conducted to evaluate the association of AT1R A1166C gene polymorphism with IgAN susceptibility. The search was performed in the databases of PubMed, Embase, and Cochrane Library as of 1 May 2014. The eligible investigations were recruited for this meta-analysis. Four literatures on the association between AT1R A1166C gene polymorphism and IgAN susceptibility were identified for this meta-analysis. Interestingly, all the included studies were from Asian population. There was no association between AT1R A1166C gene polymorphism and IgAN susceptibility for overall populations (C allele vs. A allele: OR = 1.04, 95% CI: 0.78-1.39, p = 0.76; CC vs. AC + AA: OR = 1.20, 95% CI: 0.48-2.98, p = 0.70; AA vs. AC + CC: OR = 0.97, 95% CI: 0.70-1.34, p = 0.85), and in Asians. In conclusion, AT1R A1166C gene polymorphism was not associated with IgAN susceptibility in Asian population. However, more case-control association investigations on larger, stratified populations are required in the future.

Methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism and diabetic nephropathy susceptibility in patients with type 2 diabetes mellitus.

Methylenetetrahydrofolate reductase (MTHFR) is a crucial enzyme that regulates nucleotide synthesis and DNA methylation. The MTHFR C677T gene polymorphism (rs1801133), a C → T transition at nucleotide 677 in exon 4, is a common gene variant of MTHFR and has been implicated in diabetic nephropathy, albeit with inconsistent results. Here, we performed a meta-analysis to assess the common effect size of this polymorphism on DN susceptibility. Case-control studies on the association of the MTHFR C677T gene polymorphism with DN risk were retrieved from databases up to August 1, 2013, and eligible studies were recruited into the meta-analysis and further analyzed. Of 132 studies, 33 were identified as suitable for this analysis. The results showed that T allele and TT genotype were distinctly associated with DN susceptibility in the overall population and Asians, and might be a risk factor in Caucasians and Africans (T allele: Overall population: p < 0.00001, Asians: p = 0.0002, Caucasians: p = 0.02, Africans: p < 0.00001; TT genotype: Overall population: p < 0.00001, Asians: p = 0.0003, Caucasians: p = 0.008, Africans: p = 0.0003). Furthermore, the analysis suggested that the CC genotype might play a protective role against DN onset in patients with type 2 diabetes for the overall population, Asians, Caucasian and Africans. However, due to the limited sample size in the African population, these results should be interpreted with care. In conclusion, the MTHFR C677T T allele or TT genotype might be a significant genetic molecular marker to determine the risk of DN in patients with type 2 diabetes and help to develop suitable disease prevention and management strategies.