Stromal Cell-derived Factor-1 Gene Polymorphism Research Articles

PON1, APOE and SDF-1 Gene Polymorphisms and Risk of Retinal Vein Occlusion: A Case-Control Study.

Numerous studies have tried to evaluate the potential role of thrombophilia-related genes in retinal vein occlusion (RVO); however, there is limited research on genes related to different pathophysiological mechanisms involved in RVO. In view of the strong contribution of oxidative stress and inflammation to the pathogenesis of RVO, the purpose of the present study was to investigate the association of inflammation- and oxidative-stress-related polymorphisms from three different genes [apolipoprotein E (APOE), paraoxonase 1 (PON1) and stromal cell-derived factor 1 (SDF-1)] and the risk of RVO in a Greek population. Participants in this case-control study were 50 RVO patients (RVO group) and 50 healthy volunteers (control group). Blood samples were collected on EDTA tubes and genomic DNA was extracted. Genotyping of rs854560 (L55M) and rs662 (Q192R) for the PON1 gene, rs429358 and rs7412 for the APOE gene and rs1801157 [SDF1-3'G(801)A] for SDF-1 gene was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Multiple genetic models (codominant, dominant, recessive, overdominant and log-additive) and haplotype analyses were performed using the SNPStats web tool to assess the correlation between the genetic polymorphisms and the risk of RVO. Binary logistic regression analysis was used for the association analysis between APOE gene variants and RVO. Given the multifactorial nature of the disease, our statistical analysis was adjusted for the most important systemic risk factors (age, hypertension and diabetes mellitus). The dominant genetic model for the PON1 Q192R single nucleotide polymorphism (SNP) of the association analysis revealed that there was a statistically significant difference between the RVO group and the control group. Specifically, after adjusting for age and hypertension, the PON1 192 R allele (QR + RR) was found to be associated with a statistically significantly higher risk of RVO compared to the QQ genotype (OR = 2.51; 95% CI = 1.02-6.14, p = 0.04). The statistically significant results were maintained after including diabetes in the multivariate model in addition to age and hypertension (OR = 2.83; 95% CI = 1.01-7.97, p = 0.042). No statistically significant association was revealed between the other studied polymorphisms and the risk of RVO. Haplotype analysis for PON1 SNPs, L55M and Q192R, revealed no statistically significant correlation. In conclusion, PON1 192 R allele carriers (QR + RR) were associated with a statistically significantly increased risk of RVO compared to the QQ homozygotes. These findings suggest that the R allele of the PON1 Q192R is likely to play a role as a risk factor for retinal vein occlusion.

Association of SDF-1 Gene Polymorphism with Increased Risk of Acute Myeloid Leukemia Patients.

Background:Acute myeloid leukemia (AML) is a heterogenous group of disorders that emerge from the malignant transformation of hematopoietic stem cells. Chemokine stromal cell-derived factor 1(SDF-1) and its receptor CXC receptor 4 (CXCR4) has an essential role in dissemination of blast cells. Study aimed to detect CXCR4 expression and the SDF-1 (rs1801157) gene polymorphisms and correlate them with prognosis and outcome in AML patients. Subjects and Methods:The study was conducted on 60 de-novo AML patients, and 60 healthy controls. SDF-1 (rs1801157) gene polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and CXCR4 expression was done using flow cytometry analysis. Results:SDF-1 dominant model (AG+AA) had higher risk AML (p 0.002). CXCR4 positive cases were associated significantly with toxic manifestations (p 0.019), lower CR rates (p 0.004), and unfavorable cytogenetics (p 0.027). Multivariate analysis showed that combined CXCR4positive with dominant SDF-1 considered as independent prognostic factor for shorter overall survival (OS) in AML patients (p 0.031). Conclusion:SDF-1 dominant model had a higher risk to develop AML, and CXCR4 positive expression predicts poor prognosis in AML patients and it could represent a targeted therapy in AML. In addition, CXCR4 could be easily integrated into the initial routine diagnostic work up of AML.

Effects of Complement Regulators and Chemokine Receptors in Type 2 Diabetes

ABSTRACT CD55 and CD59 are complement regulatory proteins suggested to be related with progression of diabetes and its complications. The stromal cell-derived factor 1 (SDF-1) and C-X-C chemokine receptor type 4 (CXCR-4) are chemokine proteins. We aimed to investigate the relation of CD55 and CD59 expression levels and polymorphisms of SDF-1 and CXCR-4 with type 2 diabetes mellitus (T2DM) and its complications. Seventy-five T2DM patients and 73 controls were enrolled. Expression levels of CD55 and CD59 were measured by FACS Calibur; qRT-PCR was used to determine SDF-1 and CXCR-4 gene polymorphisms. CD55 and CD59 expressions in patients with nephropathy, retinopathy and cardiovascular disease were significantly lower than controls. Frequency of CXCR-4 T allele carrying was high in patients and created 1.6 fold risk for the disease (p = .07). CXCR-4 a allele carriers had decreased nephropathy; although there was no statistical significance in carrying CXCR-4 T allele, presence of nephropathy was approximately 2 times higher (p = .254). The nephropathy risk increased 10-fold in CXCR-4 TT genotype carriers (p = .02). All SDF-1 CC genotype carriers had retinopathy, so, it was considered that the CC genotype was effective in retinopathy development (p = .031). For the presence of cardiovascular disease, significant difference was observed for SDF-1 genotypes. Increased cardiovascular risk of 5- and 1.9-fold in SDF-1 T (p = .007) and CXCR-4 T (p = .216) allele carriers, respectively, was observed. We suggest that CD55 and CD59 protein levels and SDF-1 and CXCR-4 have predictive importance in process, complications and tendency of T2DM.

SDF-1alpha G801A polymorphism in Southern Iranian patients with colorectal and gastric cancers

A single nucleotide polymorphism (SNP) in the stromal cell-derived factor-1 (SDF-1) gene at position 801 (G>A) is associated with susceptibility to certain tumors. This study aimed to investigate an association between this SNP and colorectal and gastric cancers in an Iranian population. Genotype and allele frequencies of SDF-1 801 G>A were assessed using polymerase chain reaction-restriction fragment length polymorphism in 109 patients with colorectal cancer, 124 with gastric cancer, and 262 normal control volunteers. No statistically significant difference was observed in the frequencies of genotypes and alleles between patients and controls (p > 0.05). SDF-1 gene polymorphism at position 801 (G>A) was not associated with colorectal and gastric cancers in Southern Iranian patients.

Stromal cell derived factor-1 genetic variation at locus 801 in patients with myasthenia gravis.

Myasthenia gravis (MG) is the most common disorder of neuromuscular junction in which autoantibodies develop against nicotinic acetylcholine receptor for unknown reasons. The association of immunomodulator genes with different autoimmune disease has been studied in recent years. The aim of this study was to investigate correlation between a genetic variation in Stromal Cell Derived Factor-1 (SDF1) and susceptibility to MG in an Iranian population. Genotyping of SDF1 at position 801 G/A was performed by Polymerase Chain Reaction-Restriction Length Polymorphism (PCR-RFLP) in 87 patients with confirmed myasthenia gravis and 261 normal control subjects. No statistically significant differences were observed in the frequencies of genotypes and alleles between patients and controls (p>0.05). Furthermore, no significant differences in the genotype distribution were found between the cases with different stages (p>0.05). Our data suggest that the SDF1 gene polymorphism at position 801 G/A is not associated with myasthenia gravis.

Lack of association between RANTES-28, SDF-1 gene polymorphisms and systemic lupus erythematosus in the Malaysian population

Regulated on activation, normal T-cell expressed and secreted (RANTES) and stromal cell-derived factor 1 (SDF-1) are members of the CC- and CXC-chemokine families, respectively. Both genes have been postulated to be involved in the pathogenesis of systemic lupus erythematosus (SLE). We analyzed position 28 of the RANTES gene promoter region, as well as the SNP observed in the 3' UTR of the SDF-1 gene at position 801, in 130 patients presenting SLE at the Malaya University Medical Centre. Screening of 130 healthy volunteer controls using RFLP was also performed. RANTES-28 polymorphism analysis showed no significant (P = 0.3520) relationship, even though homozygous C/C was more frequent in SLE patients (OR = 1.4183) and heterozygous C/G was more frequent in healthy controls (OR = 0.7051). There were no significant (P = 0.2650) associations between A/A (OR = 0.783), G/G (OR = 1.5914) and G/A (OR = 0.8289) genotypes in the SDF-1 gene polymorphism with SLE. We conclude that there is no significant association of RANTES-28 and SDF-1 gene polymorphisms and occurrence of SLE in Malaysia.

Stromal cell-derived factor-1 (SDF-1) alleles and susceptibility to breast carcinoma

Stromal cell-Derived Factor-1 (SDF-1, CXCL12) is one the ELR − CXC angiogenic chemokines. It contributes to hematopoiesis and lymphocyte trafficking. SDF-1 and its exclusive receptor, CXCR4, are reported to play important roles in tumor growth, angiogenesis and metastasis of different types of tumors such as breast, lung, prostate and pancreatic cancers. SDF-1 gene polymorphism, known as SDF1-3′A, has been investigated in HIV-1 infection and the incidence of breast cancer. This investigation was aimed to study the frequency of SDF1-3′A mutation in Iranian women with breast cancer. Results showed that the frequency of AA and AG genotypes was higher among patients, while the frequency of GG genotype was lower compared to the controls. Thus AA and AG genotypes of SDF-1 may be considered as factors increasing the susceptibility of Iranian women to breast cancer.

Stromal cell-derived factor-1 chemokine gene polymorphism is not associated with onset age of Japanese type 1 diabetes.

Type 1 diabetes is characterized by cell-mediated autoimmune destruction of pancreatic beta cells. Although the disease shows a strong association with HLA class II alleles, other genes may influence the initiation or the rate of progression of the autoimmune process. Recently, it was reported that a polymorphism of the stromal cell-derived factor-1 (SDF-1) (a kind of chemokine) gene was associated with early onset of type 1 diabetes in Caucasians. Therefore, we examined SDF-1 gene polymorphism in Japanese type 1 diabetes in this study. We examined the SDF-1 gene polymorphism (801G-->A) in 298 unrelated Japanese type 1 diabetic patients and 270 healthy subjects by the TaqMan PCR method. Allelic and genotypic frequencies of the SDF-1 A variants were similar in overall type 1 diabetic patients and healthy subjects. We then stratified the patients by their onset pattern (acute vs. slow onset) and islet-associated autoantibody positivity. However, no significant difference was found among each group of type 1 diabetes. Furthermore, unlike the previous report in "Caucasian" type 1 diabetics, the SDF-1 A variant was not associated with early onset of the disease in Japanese type 1 diabetics. The SDF-1 gene polymorphism was not associated with onset age (or onset pattern) of type 1 diabetes in Japanese. Further study is necessary to conclude whether SDF-1 gene polymorphism affects the onset age in type 1 diabetes in general.

Stromal-cell derived factor-1 chemokine gene variant is associated with type 1 diabetes age at onset in Japanese population

Stromal-cell derived factor-1 (SDF-1) is a powerful chemokine that upregulates T-cell migration and activation. The gene for SDF-1 is located near type 1 diabetes susceptibility locus IDDM10, suggesting a contribution by SDF-1 to the induction of diabetes. Recently the role of SDF-1 gene polymorphism in the clinical presentation of type 1 diabetes in French population has been reported. To test the putative involvement of SDF-1 gene polymorphism in predisposition to or clinical heterogeneity of type 1 diabetes in Japanese population, we conducted the case-control study. The SDF1-3′A variant (801 G to A in the 3′-untranslated region) was determined by the polymerase chain reaction–restriction fragment length polymorphism technique in 184 patients with abrupt-onset type 1 diabetes and 106 healthy control subjects. No significant difference in allele and genotype frequencies of SDF1-3′A variant was found between type 1 diabetic patients and healthy controls. However, the SDF1-3′A variant was strongly associated with early-onset diabetes in a recessive model (AA versus AG + GG, p = 0.017). The mean age-at-onset in patients carrying SDF1-3′AA genotype was significantly younger than that in patients with SDF1-3′ AG or GG genotype ( p = 0.028). The frequencies of SDF1-3′ A variant were significantly increased in HLA-DR4/9 patients compared with non-DR4/9 patients ( p = 0.008). These results suggest that the SDF-1 gene polymorphism is associated with the age-at-onset of type 1 diabetes in Japanese population.

It's moving day: factors affecting peripheral blood stem mobilization and strategies for improvement

It's moving day: factors affecting peripheral blood stem mobilization and strategies for improvement