Morphine consumption during pregnancy exacerbates neonatal hypoxia-ischemia injury in rats.

OBJECTIVE: Hypoxia-Ischemia (HI) is the most common cause of death and disability in human infants. The use of opiate in pregnant women affects their children. The aim of this study was to evaluate the effect of morphine consumption during pregnancy and lactation on vulnerability to neonatal HI in rats. MATERIALS AND METHODS: Female Wistar rats were randomly assigned into two groups: Group 1-Rats that did not receive any treatment during pregnancy and lactation and Group 2-Rats that received morphine during pregnancy and lactation. After delivery, male offspring were divided into four groups including: (a) SHAM, (b) SHAM/Morphine (SHAM/MO), (c) HI, (d) HI/Morphine (HI/MO). Seven days after HI induction, neurobehavioral tests were performed, and then, brain tissue was taken from the skull to measure cerebral edema, infarct volume, inflammatory factors, oxidative stress, and brain-derived neurotrophic factor (BDNF). RESULTS: Total antioxidant capacity (TAC) and BDNF levels in the HI/MO group were significantly lower than HI and SHAM groups. TNF-α, C-reactive protein and total oxidant capacity levels in the HI/MO group were significantly higher than HI and SHAM groups. Cerebral edema and infarct volume in the HI/MO group were significantly higher than the HI group. CONCLUSION: Based on the results, morphine consumption during pregnancy and lactation enhanced the deleterious effects of HI injury in pups.

The possible role of maternal and placental vitamin D receptor polymorphisms and haplotypes in pathogenesis of preeclampsia.

Purpose: Vitamin D deficiency may be a main causative agent in the pathogenesis of preeclampsia (PE). The actions of the active form of vitamin D are mediated via the vitamin D receptor (VDR), which is expressed in numerous organs including placenta. Therefore, we evaluated the potential relationship between maternal and placental VDR polymorphisms and the predisposition to PE in an Iranian population.Methods: This case-control study surveyed 152 PE and 160 normotensive pregnant women. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was performed to examine the maternal and placental VDR Fok1 rs2228570, Bsm1 rs1544410, Taq1 rs731236, and Apa1 rs7975232 polymorphisms.Results: The maternal but not placental VDR FokI Ff genotype, was significantly lower in PE women (P = .02 and P = .06, respectively). The maternal and placental VDR FokI polymorphism was associated with lower PE risk in the dominant model (Ff+ff vs. FF) and these genotypes could decrease PE risk (OR, 0.5 [95% CI, 0.3-0.8], P = .007 and OR, 0.5 [95% CI, 0.3-0.9], P = .02, respectively). The haplotype analysis revealed that the maternal and placental TABf haplotype may lead to decreased risk of PE. In addition, the placental TABF haplotype was associated with higher risk of PE. No relationship was observed between PE susceptibility and the maternal and placental VDR Bsm1, Taq1 and Apa1 polymorphisms. There was also no relationship between the maternal and placental VDR polymorphisms and PE severity.Conclusions: the maternal and placental VDR FokI variant was associated with decreased risk of PE in the dominant model.

Association between ERα polymorphisms and systemic lupus erythematosus: susceptibility and in silico analysis.

BACKGROUND: Systemic lupus erythematous (SLE) is a multisystem and autoimmune disorder leading to damage of multi-organ systems. The current study aimed to assess the possible association between ERα gene polymorphisms and SLE in a southeast Iranian population. METHODS: The ERα PvuII and XbaI polymorphisms were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method in 170 SLE patients and 186 healthy subjects. RESULTS: There was no association between ERα PvuII and XbaI polymorphisms and SLE susceptibility; however, the combination of the TC/AA and CC/GG genotypes of ESR α PvuII and XbaI polymorphisms were more frequent in SLE patients. The results indicated that TT haplotype of the ERα gene polymorphisms could increase the SLE risk almost 2.4-fold (odds ratio 2.4, 95% CI 1.3-4.3, P = 0.005). The in silico analysis revealed that the ERα PvuII and XbaI single nucleotide polymorphisms occurred in acceptor splicing sites, and these mutations can lead to the increase of Human Splicing Finder score of the mutant alleles. CONCLUSIONS: The ESR α PvuII and XbaI polymorphisms have no association with SLE; however, the combination of the TC/AA and CC/GG genotypes were associated with SLE susceptibility.

Effect of Achillea wilhelmsii extract on expression of the human telomerase reverse transcriptase mRNA in the PC3 prostate cancer cell line.

Evidence has indicated that human telomerase reverse transcriptase (hTERT) was overexpressed in prostate cancer (PCa). Achillea wilhelmsii (AW) is a plant that has been traditionally used for its medicinal properties. The aim of current study was to evaluate the effects of AW extract on a PCa cell line. The cytotoxic activity of the hydroalcoholic extract of AW was studied on the PCa PC3 cell line using MTT assay. Flow cytometry was used to evaluate the effects of the extract on the apoptosis. The expression of hTERT mRNA was analyzed by the reverse transcription-quantitative polymerase chain reaction method. The ELISA method was used to measure the levels of telomerase enzyme. The hydroalcoholic AW extract demonstrated the appropriate inhibitory effect in 150 µg/ml concentration (IC50) on PC3 cell line following 48 h treatment. Treatment of the PC3 cells with AW resulted in a significant increase in early and late apoptotic cells and a decrease in live cells (P<0.001), in a dose-dependent manner. Moreover, the early apoptotic cells were significantly higher than late apoptotic cells. The hTERT mRNA expression was decreased following 24 h treatment of AW extract, although it was not different between 2, 4, 8 and 12 h treatments or 24, 48 and 72 h treatments. In addition, the hTERT concentration was significantly decreased following 24 h treatment of AW extract with the marginal P-value. There was no significant difference regarding hTERT concentration between 2, 4, 8 and 12 h treatments or 24, 48 and 72 h treatments. The hydroalcoholic extract of AW induced potent antiproliferative and apoptotic effects in PC3 cell line, which could be explainable by its high potency to inhibit expression of the prominent oncogene hTERT in PCa. Therefore, targeting telomerase represents a promising strategy for PCa therapy, and AW may have considerable potential for development as a novel natural anticancer agent.

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.

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/dele-tion 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.

Interleukin-1ß (IL-1ß) & 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-1ß 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-1ß C-511T and IL-1ß 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-1ß 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-1ß C-511T polymorphism and increased risk of SLE. We observed increased frequency of CT and TT genotypes of IL-1ß C-511T polymorphism in SLE patients with malar rash compared to SLE patients without this manifestation. INTERPRETATION & CONCLUSIONS: The present findings suggest that IL-1ß T-31C and IL-4 VNTR polymorphisms but not IL-1ß C-511T polymorphism may contribute in SLE pathogenesis. In addition, CT and TT genotypes of IL-1ß C-511T polymorphism were associated with SLE.

Association of the osteopontin rs1126616 polymorphism and a higher serum osteopontin level with lupus nephritis.

Osteopontin (OPN) is a chemokine-like glycoprotein that has a prominent role in regulating inflammation and immunity. OPN polymorphisms and elevated OPN levels are associated with systemic lupus erythematosus (SLE) in several populations. The aim of present study was to evaluate the association between the OPN rs1126616 polymorphism and OPN level with SLE susceptibility. A total of 163 SLE patients and 180 age-, gender- and ethnically matched controls were genotyped for the rs1126616 polymorphism by the polymerase chain reaction-restriction fragment length polymorphism method. Serum OPN levels were assayed by the enzyme-linked immunosorbent assay. There was no association between the OPN rs1126616 C/T polymorphism and SLE. The frequency of the OPN rs1126616 CT genotype was significantly higher in SLE patients with nephritis compared to SLE patients without nephritis and controls. Additionally, the frequency of TT genotypes was higher in SLE patients with nephritis compared to controls. The serum OPN levels were significantly higher in SLE patients compared to controls (50.6±22 vs. 35.6±15.8 ng/ml, P<0.001). Increased serum OPN levels were observed in SLE patients with lupus nephritis and joint symptoms. There was no correlation between OPN levels and the OPN rs1126616 polymorphism. The present data suggest that the CT and TT genotypes of the OPN rs1126616 polymorphism could be a risk factor for lupus nephritis. The OPN level is associated with SLE and certain SLE manifestations. However, there was no association between the OPN rs1126616 C/T polymorphism and 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.

Association of interleukin-1 receptor antagonist VNTR polymorphism and risk of pre-eclampsia in southeast Iranian population.

AIM: Pre-eclampsia (PE) is an obstetric disorder that may result in maternal and neonatal mortality and morbidity. Growing evidence indicates that cytokines, such as interleukins, are involved in the pathogenesis of this complication. Hence the current study aimed to assess the possible association between interleukin-1 receptor antagonist (IL-1Ra) VNTR polymorphism, and PE susceptibility in southeast Iranian women. MATERIAL AND METHODS: The IL-Ra VNTR polymorphism was evaluated in 192 PE women and 186 age-matched normotensive pregnant women by the polymerase chain reaction method. RESULTS: The frequency of the A2 allele and the A2A2 genotype of IL-Ra VNTR polymorphism was significantly lower in PE patients compared to controls: therefore, A2 allele may play a protective role in PE development (odds ratio = 0.13 95% CI, [0.04-0.03]; P < 0.0001). In addition, there was no relation between the IL-Ra VNTR polymorphism and severity of the disease. CONCLUSION: The A2 allele of the IL-Ra VNTR polymorphism could be a protective factor for PE susceptibility.

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

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.

Combination Effect of GSTM1, GSTT1 and GSTP1 Polymorphisms and Risk of Systemic Lupus Erythematosus.

BACKGROUND: Progression of systemic lupus erythematosus (SLE) could be due to oxidative stress especially through reactive oxygen species (ROS). Detoxification of ROS is largely performed by Glutathione S-transferases (GSTs), therefore polymorphisms of GSTM1, GSTT1 and GSTP1 genes which decrease enzymes activity could affect SLE susceptibility. The aim of this study was to determine the effects of GSTM1 (deletion), GSTT1 (deletion) and GSTP1 (Ile105Val) polymorphisms on SLE susceptibility. METHODS: Genomic DNA was extracted from blood samples of 163 SLE patients and 180 age, sex and ethnically matched controls. GSTs genotypes were determined by polymerase chain reaction (PCR)-multiplex procedure or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: GSTT1 null genotype frequency was higher in SLE patients than controls. NO association observed between GSTM1 null genotype or GSTP1 Ile105Val polymorphism with SLE. Nevertheless combination of GSTT1 null/ GSTM1 null genotypes showed 2.8-fold increase in risk of SLE. Moreover the combination of GSTT1 null/ GSTM1 null/GSTP1 Ile/Val and Val/Val genotypes increased the SLE risk about 8 fold. CONCLUSION: Present data suggest that GSTT1 null/ GSTM1 null/GSTP1 Ile/Val and Val/Val genotypes might largely contribute to the pathogenesis of SLE.

Association between vitamin D receptor polymorphisms and haplotypes with pulmonary tuberculosis.

The vitamin D receptor (VDR) is an important factor in activating immune response in different infectious diseases. The aim of the present study was to investigate the association between the VDR gene polymorphisms and pulmonary tuberculosis (PTB). The case control study was performed on 120 PTB patients and 131 healthy controls. Genetic analysis was performed by polymerase chain reaction and the restriction fragment length polymorphism method. The VDR Fok1 Ff genotype was associated with TB and the risk of PTB was two times higher in individuals with the Ff genotype. A higher frequency of f allele was observed in PTB patients and therefore, the f allele may be a risk factor for PTB susceptibility. There were no associations between the Taq1 and Bsm1 polymorphisms and PTB. In addition, haplotype analysis showed that the f-T-B and f-t-b haplotypes (Fok1, Taq1 and Bsm1) may have the potential to increase PTB susceptibility. In conclusion, the Ff genotype and f allele of the VDR Fok1 polymorphism were associated with PTB susceptibility. In addition, the f-T-B and f-t-b haplotypes may be the susceptible haplotypes for PTB.

The early-onset preeclampsia is associated with MTHFR and FVL polymorphisms.

PURPOSE: The aim of this study was to examine the association of factor V Leiden, prothrombin and methylenetetrahydrofolate reductase (MTHFR) polymorphisms and preeclampsia (PE) in Southeast of Iran. METHODS: This case-control study was performed on 192 preeclamptic and 196 normotensive pregnant women. Single nucleotide polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Tetra ARMS methods. RESULTS: No significant differences were observed in distribution of MTHFR C677T and FVL polymorphisms between two groups. There was a significant difference in frequency of 1298AC genotype in PE pregnant women compared to controls (P = 0.03). No 20210A allele of prothrombin gene was observed in this population. The analysis of MTHFR and factor V Leiden polymorphisms between early-onset PE (EOPE) and late-onset PE (LOPE) showed significant differences in MTHFR A1298C polymorphism (AC and CC vs AA, P = 0.012 and P = 0.006, respectively) and G1691A polymorphism of FVL(GA vs GG, P = 0.03). Moreover, the analysis of three SNPs between EOPE and controls showed significant differences in MTHFR C677T (CT + TT vs CC, P = 0.035) and MTHFR A1298C (AC and CC vs AA, P = 0.001 and P = 0.006, respectively) polymorphisms. The synergic effect of MTHFR A1298C and C677T polymorphisms showed increased risk of EOPE. CONCLUSION: MTHFR A1298C polymorphism was associated with PE. Although MTHFR C677T and FVL polymorphisms did not differ between PE patients and controls, significant differences in MTHFR A1298C, C677T and FVL polymorphisms between EOPE and LOPE/controls were observed. The synergic effect of MTHFR variants could increase PE and EOPE risk.

Association of functional polymorphisms in FAS and FAS Ligand genes promoter with pre-eclampsia.

AIM: Pre-eclampsia (PE) is a complex disorder of pregnancy with unknown etiology. FAS-mediated apoptosis is assumed to prevent the development of PE; therefore FAS and FAS Ligand may be represented as candidate genes involved in PE pathogenesis. In the present study, we evaluated the relation between FAS Ligand A-670G (rs1800682) and FAS Ligand C-844T (rs763110) gene polymorphisms with PE in southeast Iran. METHODS: One hundred and twenty-seven unrelated women with PE and 139 healthy control subjects were genotyped for the FAS A-670G and FAS Ligand C-844T polymorphisms by polymerase chain reaction restriction fragment length polymorphism method. RESULTS: The AA, AG and GG genotype frequency of the FAS A-670G polymorphism were 21.3%, 53.5% and 25.2% in pre-eclamptic women and 46.0%, 41.5% and 11.5% in controls and were statistically different (P = 0.0001). The risk of PE was 2.7- and 4.7-fold higher in pregnant women with AG and GG genotypes respectively. Although the frequency TT genotype and T allele of FAS Ligand C-844T gene polymorphism was higher in the PE group, the differences were not significant. CONCLUSION: FAS A-670G polymorphism is associated with a higher risk for PE. There was no association between FAS Ligand C-844T polymorphism and PE.

KE and EE genotypes of ICAM-1 gene K469E polymorphism is associated with severe preeclampsia.

BACKGROUND: Preeclampsia (PE) is one of the most important complications of pregnancy that is associated with significant mortality and morbidity in mother and fetus. Since the etiologic factors in its development are still unclear, we aimed to examine the intercellular adhesion molecule-1 (ICAM-1) gene K469E polymorphism in preeclamptic and control healthy women. MATERIALS AND METHODS: Genetic polymorphism was analyzed in 192 PE and 186 healthy control women. PCR-RFLP method was used to identify K469E polymorphism. RESULTS: The frequency of KK, KE, and EE genotypes of ICAM-1 gene was not different between PE patients and healthy pregnant women. Whereas, the frequency of KE and EE genotypes was significantly higher in severe PE than mild PE women and control group, and the risk of severe PE was 2.4-fold higher in subjects with KE genotype (OR, 2.4 [95% CI, 1 to 5.9]; P = 0.03) and 3.3-fold higher in subjects with EE genotype (OR, 3.3 [95% CI, 1.2 to 9]; P = 0.015) compared to individuals with KK genotype. CONCLUSION: We concluded that KE and EE genotypes of K469E polymorphism could increase risk of severe PE.

Different profile of serum leptin between early onset and late onset preeclampsia.

AIM: This study was designed to clarify the role of leptin and adiponectin in preeclampsia (PE) pathogenesis and different subtypes of preeclampsia. METHOD: This case control study was performed in 45 PE patients and 45 healthy controls matched for age, BMI, and ethnicity. Serum leptin and adiponectin levels were determined by enzyme linked immunosorbent assay (ELISA). RESULTS: Maternal serum leptin and adiponectin were significantly higher in PE women than controls. Serum leptin was elevated in early onset preeclampsia (EOPE) and late onset preeclampsia (LOPE) compared to controls. Among PE patients, serum leptin was higher in EOPE than LOPE women. However, serum adiponectin was not different between EOPE and LOPE women. The serum leptin was significantly higher in severe PE than mild PE. The serum adiponectin was significantly elevated in severe PE compared to controls. Significant positive correlation was observed between leptin and adiponectin and also between leptin and BMI in controls. Moreover significant positive correlation was observed between adiponectin and BMI in PE patients and controls. CONCLUSION: The present study showed that serum leptin level may play a significant role as a biomarker to differentiate early and late onset PE and also its relation to BMI and severity of disease.

Association of FAS and FAS ligand genes polymorphism and risk of systemic lupus erythematosus.

UNLABELLED: 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.

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.