Toll-like Receptor 1 Polymorphisms Increased the Risk of Pulmonary Tuberculosis in an Iranian Population Sample / 生物医学与环境科学（英文）

A case-control study was carried out that involved 203 individuals diagnosed with pulmonary tuberculosis (PTB) and 203 healthy subjects. Genotyping of TLR1 rs5743551 and rs5743618 polymorphisms was done using polymerase chain reaction-restriction fragments length polymorphism assay. We found that TLR1 rs5743551 variant affected the risk of PTB in the codominant (OR=3.28, 95% CI=1.98-5.45, P<0.0001, GA vs. GG; OR=1.86, 95% CI=1.05-3.28, P=0.033, AA vs. GG) and dominant (OR=2.69, 95% CI=1.67-4.34, P<0.0001, GA+AA vs. GG) inheritance models tested. The A allele was associated with a higher risk of PTB than the G allele (OR=1.33, 95% CI=1.01-1.75, P=0.049). The TG genotype of the rs5743618 variant significantly increased the risk of PTB compared to the risk associated with the TT genotype (OR=3.29, 95% CI=1.82-5.97, P<0.0001). The G allele was associated with a higher risk of PTB than the T allele (OR=3.00, 95% CI=1.69-5.31, P=0.0001). Our findings revealed that TLR1 rs5743551 and rs5743618 polymorphisms affected the risk of PTB in an Iranian population sample. Additional studies with larger sample sizes and involving subjects of different ethnicities are required to validate our present findings.

TIRAP rs8177374 gene polymorphism increased the risk of pulmonary tuberculosis in Zahedan, southeast Iran

OBJECTIVE@#To evaluate the possible association between Toll-interleukin 1 receptor (TIR) domain containing adaptor protein (TIRAP; also known as MAL) rs1893352 and rs8177374 (S180L) gene polymorphisms and pulmonary tuberculosis (PTB) in a sample of Iranian population.@*METHODS@#This case-control study was performed on 174 PTB and 177 healthy subjects. Tetra amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) was used to detect the polymorphisms.@*RESULTS@#Our finding showed that neither the overall Chi-square comparison of PTB and control subjects nor the logistic regression analysis indicated any association between rs1893352 polymorphism and PTB. Regarding rs8177374 polymorphism, the CT genotype as well as CT+TT increased the risk of PTB in comparison with CC genotype (OR=4.73, 95% CI=2.65-8.45, P<0.0001 and OR=6.47, 95% CI=3.68-11.38, P<0.0001, respectively). The rs8177374 T allele increased the risk of PTB in comparison with C allele (OR=4.21, 95% CI=2.43-7.26, P<0.0001).@*CONCLUSIONS@#Our finding indicates that TIRAP rs8177374 polymorphism is associated with PTB in a sample of Iranian population.

40-bp insertion/deletion polymorphism of murine double minute2 [MDM2] increased the risk of breast cancer in Zahedan, southeast Iran

MDM2 [Murine Double Minute2] is an oncoprotein that inhibits the P53 activity. Overexpression of MDM2 gene has been reported in several human tumors. In the present study, we aimed to evaluate the impact of 40-bp insertion/deletion [ins/del] polymorphism on the promoter of MDM2 and susceptibility to breast cancer in a sample of Iranian population. Methods: This case-control study was carried out on 236 patients with breast cancer and 203 healthy individuals. Genomic DNA was extracted from the whole blood by the salting-out method. The 40-bp ins/del polymorphism was determined by using polymerase chain reaction. The findings indicated that MDM2 ins/del variant increased the risk of breast cancer in co-dominant- [odds ratio [OR] = 2.09, 95% CI = 1.14-3.85, P = 0.018, del/del vs. ins/ins], dominant- [OR = 1.49, 95% CI = 1.02-2.18, P = 0.038, ins/del + del/del vs. ins/ins], and recessive- [OR = 1.86, 95% CI = 1.03-3.34, P = 0.038, del/del vs. ins/ins + ins/del] tested inheritance models. The del allele increased the risk of breast cancer [OR = 1.48, 95% CI = 1.11-1.98, P = 0.008] compared with ins allele. Our result revealed that 40-bp ins/del polymorphism in the promoter of MDM2 increased the risk of breast cancer in an Iranian population. Further investigations with larger sample sizes and diverse ethnicities are needed to verify our findings

CD226 rs763361 [Gly307Ser] polymorphism is associated with susceptibility to rheumatoid arthritis in Zahedan, southeast Iran

Rheumatoid arthritis [RA] is a chronic inflammatory disease with many genetic factors predisposing to disease susceptibility. The aim of the present study was to investigate the impact of CD226 rs727088 and rs763361 polymorphisms and susceptibility to RA in a sample of the Iranian population. This case-control study was carried out on 100 patients with RA and 104 healthy subjects. The polymorphisms were determined using tetra amplification refractory mutation system-polymerase chain reaction assay. The rs763361 [Gly307Ser] polymorphism increased the risk of RA in codominant, dominant and recessive-tested inheritance models [odds ratio [OR] = 3.18, 95% confidence intervals [95% CI] = 1.44-7.02, P = 0.004, CC vs. TT, and OR = 1.98, 95% CI = 1.10-3.57, P = 0.023, CC vs. CT-TT, and OR = 2.61, 95% CI = 1.26-5.37, P = 0.010, CC + CT vs. TT, respectively]. In addition, the rs763361 T allele increased the risk of RA [OR = 2.06, 95% CI = 1.38-3.08, P<0.001]. However, no significant difference was observed among the groups regarding CD226 rs727088 polymorphism [Chi[2] = 3.20, P = 0.202]. Our finding showed that CD226 rs763361, but not rs727088, gene polymorphism increased the risk of RA in a sample of the Iranian population

Anti-HLA antibodies and kidney allograft outcomes in recipients with donor bone marrow cell infusion

Anti-HLA-antibodies are known to affect the allograft survival in transplant recipient patients. The aim of this study was to evaluate the association between anti-HLA antibodies and kidney allograft outcomes, particularly in recipients with concurrent donor bone marrow cell infusion [DBMI]. Between June 2006 and May 2007, forty living unrelated donor kidney transplants consisting of 20 recipients with DBMI and 20 without infusion entered into the study and were monitored prospectively for one year. Pre-and post-transplant [days 14, 30, and 90] sera were screened for the presence of anti-HLA class-I and II antibodies, and subsequently positive sera retested with ELISA specific panel for antibody specification. Of 40 patients, 9 [22.5%] experienced acute rejection episodes [ARE] [6/20 cases in non-infused versus 3/20 in DBMI patients]. The prevalence of anti-HLA antibodies before and after transplantation were higher in patients with ARE compared to non-rejecting ones [88.8% vs. 38.7%, p=0.01 and 66.6% vs. 25.8%, p=0.04, respectively]. A total of 10% [4/40] of patients developed donor specific anti-HLA antibodies [DSA] and in this regard 2 patients from the control group experienced ARE. All 3 rejecting patients in DBMI group were negative for DSA and positive for non-DSA. The lower titer of post-transplant anti-HLA antibodies were shown in DBMI patients compared to pre-transplantation titer. Additionally, the average serum creatinine levels during one year follow up and even in those patients with ARE were lower compared to controls. Our findings reveal an association between pre-and post-transplant anti-HLA antibodies, and ARE and also early allograft dysfunction. It suggests that lower incidence of ARE, undetectable DSA, lower titer of antibodies concomitant with a decrease in serum creatinine level, better allograft function and lower percentages of PRA in DBMI patients, could be the probable manifestations of partial hypo-responsiveness against allografts

Posttransplant infectious complications: a prospective study on 142 kidney allograft recipients

We evaluated the posttransplant complications resulting from infections and their association with graft function, immunosuppressive drugs, and mortality. A total of 142 kidney allograft recipients were followed for 1 year after transplantation. The patients' status was assessed during regular visits, and data including clinical characteristics, infections, serum creatinine level, acute rejection episodes, immunosuppressive regimen, graft function, and mortality were recorded and analyzed. Infections occurred in 77 patients [54%]. The lower urinary [42%] and respiratory [6.3%] tracts were the most common sites of infection. The most frequent causative organisms were Klebsiella in 34 [24%] and cytomegalovirus in 25 patients [18%]. Wound infection occurred in 7 patients [5%]. The mortality rate was 7.7% and infection-related death was seen in 5 patients [3.5%] who developed sepsis. Graft loss was seen in 16 patients [11%], of whom 2 developed cytomegalovirus infection, 2 experienced urinary tract infection, and 5 developed sepsis and died. Mycobacterial and hepatitis C infections were noticeably rare [0.7% and 2.8%, respectively]. This study showed that infections are important causes of morbidity and mortality during the posttransplant period. We recommend that serologic tests be performed before and after transplantation to recognize and meticulously follow those who are at risk. In our study, high-risk patients were those with elevated serum creatinine levels who received high doses of immunosuppressive drugs. As the urinary tract is the most common site of infection, early removal of urethral catheter is recommended to reduce the risk of infection