Association of FAS and FAS Ligand Genes Polymorphism and Risk of Systemic Lupus Erythematosus

FAS/FASL pathway plays a critical role in maintaining peripheral immune tolerance; therefore, the apoptosis genes, Fas and Fas ligand (FasL), could be suitable candidate genes in human SLE susceptibility. Materials and Methods. In this case-control study, 106 SLE patients and 149 sex, age, and ethnicity matched healthy controls were genotyped for the Fas A-670G and FasLC-844T polymorphisms by polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP). Results. The frequency of -670AA genotype was significantly higher in SLE patients than control group and the risk of SLE was 2.1-fold greater in subjects with AA genotype (P=0.03). The frequency of -670A allele was significantly higher in SLE patients than in controls too (58% versus 49%, P=0.03). The -844CC genotype frequency was significantly higher in SLE patients than in healthy controls and the risk of SLE was 2.8-fold greater in these subjects (P=0.01). The C allele frequency was significantly higher in patients than in controls (69% versus 49%, P=0.001). Increased SLE risk was observed in individuals with combined effect of Fas-670AA and FasL-844CC genotypes (P=0.001). Conclusion. Fas-670AA and FasL-844CC genotypes were associated with SLE risk, and combined effect of -670AA and -844CC genotypes might increase SLE susceptibility

Prooxidant-Antioxidant Balance in Patients with Systemic Lupus Erythematosus and Its Relationship with Clinical and Laboratory Findings

Aim. This study was aimed at evaluating prooxidant-antioxidant balance (PAB) in patients with systemic lupus erythematosus (SLE) and its relationship with laboratory findings and clinical manifestations. Methods. In this case-control study, 60 patients with SLE and 60 healthy individuals were enrolled. The blood samples were collected and their sera were separated. Subsequently, the prooxidant-antioxidant balance value was evaluated using PAB assay for each sample. Results. The mean of PAB values in SLE patients was significantly higher than healthy controls (147.3±42 versus 84.8±32.2 HK, P<0.0001). Furthermore, in SLE patients, there was a positive significant correlation between the PAB and erythrocyte sedimentation rate (ESR) (r=0.492, P<0.001). In addition, the PAB values in patients with alopecia, discoid rash, oral ulcers, arthritis, and nephritis were significantly higher than those without these manifestations. Conclusion. The findings of current study showed that the mean of PAB was significantly higher in SLE patients and PAB was correlated with ESR. Moreover increased PAB was found in SLE patients with alopecia, discoid rash, oral ulcers, arthritis, and nephritis. These findings suggest that the measurement of PAB may be useful to show oxidative stress condition in SLE patients

The −2549 insertion/deletion polymorphism of VEGF gene associated with uterine leiomyoma susceptibility in women from Southeastern Iran

Objectives: Vascular endothelial growth factor (VEGF) is an important angiogenic factor that regulates angiogenesis and mediates sex steroid-induced cell growth. The present study investigated the association of VEGF gene-2578C/A (rs699947) and −2549 insertion/deletion polymorphisms in the promoter region of VEGF-A gene and uterine leiomyoma susceptibility in Southeast of Iran. Material and methods: One hundred and fifty five women with uterine leiomyoma and 157 age, BMI, and ethnicity matched healthy women were enrolled in this study. VEGF gene –2578C/A polymorphism genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, and the –2549 insertion/dele­tion polymorphism was analyzed by PCR method. Results: The frequency of alleles and genotypes of VEGF-2578C/A polymorphism was not different between women with uterine leiomyoma and the controls; however, a significant association was revealed between II genotype of –2549 insertion/deletion (I/D) polymorphism of VEGF gene and uterine leiomyoma. Conclusions: The findings showed that VEGF gene –2549 insertion/deletion polymorphism was associated with uterine leiomyoma

Association of XRCC1 Arg399GIn and Tp53 Arg72Pro polymorphisms and increased risk of uterine leiomyoma - A case-control study

Abstract The aim of present study was to investigate the role of the X-ray repair cross-complementing protein1 (XRCC1) and Tumor protein p53 (Tp53) polymorphisms in Uterine Leiomyoma (UL) susceptibility in southeastern Iran. This case control study was performed on 139 women with UL and 149 age, BMI and ethnicity matched healthy women. All women were genotyped for the XRCC1 Arg399Gln, XRCC1 Arg194Trp and Tp53 Arg72Pro polymorphisms. The frequency of Tp53 72 Pro/Pro genotype was significantly higher in UL women compared to controls. The risk of UL was 1.5 fold higher in women with the Pro/Pro genotype (OR, 1.5 [95% CI, 1.1 to 2.1], p = 0.012). Moreover, the frequency of the Pro allele was significantly higher in the UL women. Although the frequency of XRCC1 Arg399Gln genotypes did not significantly differ between UL and control groups before adjusting for age, there was an association between the XRCC1 Arg/Gln genotype and UL after adjusting for age (OR, 1.8 [95% CI, 1.1 to 3]). No association was observed between the XRCC1 Arg194Trp polymorphism and UL. The Pro/Pro genotype of Tp53 Arg72Pro polymorphism was associated with UL susceptibility. In addition, the XRCC1 Arg/Gln genotype was associated with increased risk of UL after adjusting for age

Estrogen receptor alpha XbaI GG genotype was associated with severe preeclampsia

Purpose: Estrogen receptor-α (ERα) plays an essential role in the adaptation of increased uterine blood flow during gestation. Therefore, ERα gene could be a possible candidate for preeclampsia (PE) susceptibility. In current study we aimed to investigate the association of the ERα gene polymorphisms and PE in an Iranian population. Methods: A total of 192 pregnant women with PE and 186 normotensive women were genotyped for ERα gene (PvuII and XbaI) polymorphisms by polymerase chain reaction-restriction fragment length polymorphism method. Results: The frequencies of alleles and genotypes of ERα PvuII and XbaI polymorphisms were not different between PE and normotensive control women. However, higher frequency of GG genotype was observed in women with severe PE compared to mild PE (OR, 1.8 [95% CI, 1.1 to 3]; p = 0.02) and in severe PE compared to normotensive women [OR = 1.8 (1.1–3), p = 0.02] after adjusting for age, ethnicity, and primiparity. Conclusions: The GG genotype of ERα XbaI polymorphism could be a genetic risk factor for PE predisposition

Association between TLR4 and TLR9 Gene Polymorphisms with Development of Pulmonary Tuberculosis in Zahedan, Southeastern Iran

Some evidence suggests that a variety of genetic factors contribute to development of the tuberculosis (TB). TLR4 and TLR9 have been proposed as susceptibility genes for TB. This study was performed in 124 newly diagnosed TB cases and 149 healthy controls in a TB-endemic region of Iran. The TLR4 genes Asp299Gly, Thr399Ile, and TLR9 gene T-1486C polymorphisms were amplified by polymerase chain reaction (PCR) and then detected by PCR-restriction fragment length polymorphism (RFLP). The frequencies of the mutant alleles of TLR4 Arg299Gly, Thr399Ile, and TLR9 T-1486C polymorphisms were 0.8 versus 0.1, 5.6 versus 3, and 28.6 versus 25.2 in patients and controls, respectively, that were not significant. The synergic effect of TI,II/CC genotypes for TLR4 Thr399Ile and TLR9 T-1486C polymorphisms showed increased risk of PTB susceptibility. In conclusion, no significant relation was found between TLR4 and TLR9 polymorphisms alone and PTB. However, synergic effects of TLR4 Thr399Ile and TLR9-1486T/C polymorphisms might increase risk of PTB

Interleukin-1β (IL-1β) & IL-4 gene polymorphisms in patients with systemic lupus erythematosus (SLE) & their association with susceptibility to SLE

Background & objectives: Interleukin-1 (IL-1) is one of the pro-inflammatory cytokines that plays a main role in the regulation of immune and inflammatory responses. Interleukin 4 (IL-4) as an anti-inflammatory cytokine regulates balance between Th1 and Th2 immune responses. this study was undertaken to investigate the IL-1β and IL-4 genes polymorphisms in patients with systemic lupus erythematosus (SLE) and also association between the polymorphisms and susceptibility to SLE. Methods: One hundred and sixty three SLE patients and 180 healthy controls were genotyped for the IL-4 VNTR (variable number tandem repeat), IL-1β C-511T and IL-1β T-31C polymorphisms by polymerase chain reaction (PCR) or PCR-RFLP (restriction fragment length polymorphism) method. Results: The frequencies of CC genotype and C allele of the IL-1β T-31C polymorphism were significantly (P<0.01) lower in SLE patients than controls. Moreover, the frequencies of RP1/RP2 genotype and RP2 allele of IL-4 VNTR polymorphism were significantly (P<0.05) higher in the SLE patients. No association was observed between IL-1β C-511T polymorphism and increased risk of SLE. We observed increased frequency of CT and TT genotypes of IL-1β C-511T polymorphism in SLE patients with malar rash compared to SLE patients without this manifestation. Interpretation & conclusions: The present findings suggest that IL-1β T-31C and IL-4 VNTR polymorphisms but not IL-1β C-511T polymorphism may contribute in SLE pathogenesis. In addition, CT and TT genotypes of IL-1β C-511T polymorphism were associated with SLE