فهرست مطالب ziba rahimi

Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. The MDM2 and p53 are interacting proteins that play crucial roles in cell biology. Genetic variations of p53 and MDM2 have been identified in many cancers including CLL; among which are SNP309 in the promoter of MDM2 and SNP codon72 in p53.

In this study, we sought to find the impact of two SNPs of p53 and MDM2 in the pathogenesis of CLL. A total of 100 CLL patients and 102 healthy controls were recruited. Genomic DNA was extracted, and genotyping was performed using the PCR-RFLP method. The allele and genotype associations were analyzed using the χ2 test. The gene-gene interaction analysis was studied using GMDR v0.9.

Our study found the absence of a significant difference between CLL patients and controls related to the allelic frequencies or genotypic distributions for both MDM2 SNP309 and p53 codon72. A significantly higher frequency of p53 C allele was found in patients with disease duration of more than 36 compared to those less than 36 months. However, GMDR analysis suggests genetic interaction between the genes under study.

Our findings indicated each polymorphism of p53 codon72 and MDM2 (SNP309) was not a risk factor for CLL but the p53 C allele could be associated with the disease duration. Besides, the interaction between p53/MDM2 genotypes may confer susceptibility to CLL. Our study could be useful in genetic association studies of CLL and the role of gene-gene interactions in the susceptibility to the disease.

Breast cancer (BC) is known to be the most prevalent cancer among women. One-carbon metabolism (OCM) disturbance might play an important role in the etiology of BC. The present study aimed to investigate the thymidylate synthase (TYMS), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), and methionine synthase reductase (MTRR) variants as good candidates for studying the role of genetic variants of folate metabolizing enzymes in the risk of BC.

The present case-control study consisted of 100 BC patients and 141 healthy females. The TYMS 2R/3R (rs34743033), MTR c.2756A>G (rs1805087), and MTRR c.66A>G (rs1801394) variants were detected by polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism (RFLP), and a designed amplification-refractory mutation system (ARMS) method, respectively.

The 3R allele of TYMS enhanced the risk of BC by 2.84-fold (p <0.001). In the presence of TYMS 3R/3R, compared to TYMS 2R/3R, there was a trend toward enhancing the risk of metastasis by 4.15-fold (95% CI: 0.96-17.85, p =0.055). The frequencies of MTR c.2756A>G and MTRR c.66A>G variants were not significantly different among patients and controls.

We observed that the TYMS 3R is a risk allele for susceptibility to BC and this allele tends to increase the BC metastasis.

To find an association between gene variants of insulin-like growth factor-1 (IGF-1) and 5,10-methylenetetrahydrofolate reductase (MTHFR) with the risk of acne vulgaris (AV).

In a case-control study, we investigated 150 AV patients and 148 healthy individuals (aged 18-25 years) for the IGF-1 G>A and MTHFR C677T polymorphisms, as well as the serum levels of IGF-1, insulin, and the homeostasis model assessment of insulin resistance (HOMA-IR). The serum biochemical parameters and the genotypes of IGF-1 G>A and MTHFR C677T were detected by using appropriate kits and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods, respectively.

The frequencies of IGF-1 and the MTHFR polymorphisms were not significantly different comparing patients and controls. The serum level of IGF-1 was 179.8±72.8 µg/L in AV patients compared to 164.6±63.7 µg/L in controls (P=0.056). The serum level of insulin in female patients was significantly higher than controls. The HOMA was 3.54±5.6 in patients compared to 1.16±1.4 (P<0.001) in controls. Significantly higher levels of fasting blood sugar (FBS), total cholesterol, and low-density lipoprotein-cholesterol (LDL-C) were detected in female patients than controls. However, the level of estradiol was significantly lower in female patients than in controls. In females, the presence of the MTHFR T allele was associated with significantly higher levels of FBS and LDL-C, as well as a significantly lower level of estradiol compared to those carriers of the C allele.

We found the absence of an association between IGF-1 and MTHFR polymorphisms with the risk of AV. However, increased insulin, IGF-1, and HOMA levels in AV patients indicated the effect of insulin and insulin resistance in the risk of AV and its severity.

Acne vulgaris (AV) is a common skin disease that causes physical and psychological problems for affected individual. In addition to systemic changes in hormone levels, overproduction of local steroids, especially androgens are associated with AV. Cytochrome (CYP) 19 is involved in the synthesis of estrogens. The aim of the present study was to investigate the influence of CYP19A.

The key enzyme of methylenetetrahydrofolate reductase (MTHFR) is involved in DNA biosynthesis and repair. The role of MTHFR C677T polymorphism in susceptibility to breast cancer is controversial. In the present case-control investigation, 297 individuals consisted of 100 patients with breast cancer and 197 healthy women were studied for MTHFR C677T genotypes, using PCR-RFLP method. The frequency of MTHFR TT genotype was 10% in patients and 3% in controls (P = 0.008). The presence of TT genotype was associated with susceptibility to breast cancer [OR = 1.97, 95%CI: 1.16-3.36, P = 0.012]. The T allele of MTHFR was found in 30% of the patients compared to 27.6% healthy controls (P = 0.024) that enhanced the risk of breast cancer by 1.56 times (95% CI: 1.06 - 2.3, P = 0.024). There were 71 individuals (71%) with the age of breast cancer diagnosis ≤ 51 years old. Comparing patients with the age of cancer diagnosis ≤ 50 years old with those > 51 years old group indicated a higher frequency of MTHFR TT genotype in the latter (20.7%) compared to the first group (5.6%, P = 0.05). Our study demonstrated an association between the MTHFR C677T polymorphism with the risk of breast cancer among population of Western Iran. Also, our study suggests that the MTHFR TT genotype could be a risk factor for breast cancer in postmenopausal women.

The aim of present study was to clarify the role of the peroxisome proliferator-activated receptor (PPAR) γ Pro12Ala and C161T polymorphisms in the pathogenesis of polycystic ovary syndrome (PCOS) and their influence on lipid and lipoprotein profiles of patients.
The present cross-sectional study consisted of 50 women with PCOS, who referred to the Kermanshah University of Medical Sciences Clinic between April and October 2015, and 233 unrelated age-matched healthy women from the same region (West Iran). The PPARγ Pro12Ala and PPARγ C161T polymorphisms were gen- otyped using the polymerase chain reaction-restriction fragment length polymorphism method. Fasting blood sugar (FBS), serum triglycerides (TG), cholesterol, low density lipoprotein- cholesterol (LDL-C), high density lipoprotein- cholesterol (HDL-C) and estradiol levels were measured.
The serum level of estradiol was significantly lower in PCOS patients compared to healthy women. The PPARγ Pro12Ala (CG) genotype increased the risk of PCOS 2.96-fold. The frequency of the PPARγ T allele (at C161T) was 21% in patients and 17.2% in controls with no significant difference (P=0.52). In all studied individuals, the PPARγ CG geno- type was associated with significantly higher levels of TG. However, significantly lower levels of total cholesterol and LDL-C were observed in PPARγ TT individuals compared with those with the CC genotype. Within the PCOS group, the PPARγ CG genotype was significantly associated with lower levels of estradiol compared with the CC genotype. Also, the CG genotype was significantly associated with higher levels of TG when compared with the CC genotype.
Our study shows that, unlike PPARγ C161T, PPARγ Pro12Ala is associated with the risk of PCOS. Also, we found that the lipid and lipoprotein profiles significantly vary based on PPARγ Pro12Ala and C161T genotypes.

The variants of angiotensin converting enzyme (ACE) and matrix metalloproteinases (MMPs) genes might be involved in the pathogenesis of end stage renal disease (ESRD) and hypertension. We studied the ACE insertion/deletion (I/D) and MMP-7 A-181G variants in 99 unrelated ESRD patients and 117 individuals without renal complications from Western Iran with Kurdish ethnic background. The frequency of ACE I/D variants was not significantly different between ESRD patients and controls. However, the presence of ACE D allele increased the risk of hypertension in ESRD patients by 2.14-fold (P=0.036). The MMP-7 -181 AG genotype increased the risk of ESRD by 2.04 times (P=0.026). The present study indicated the absence of an association between the ACE I/D polymorphism with the risk of ESRD. However, the ACE D allele increased the risk of hypertension in ESRD patients. Also, the present study suggests a role for MMP-7 AG genotype in the pathogenesis of ESRD.

Brain-derived neurotrophic factor (BDNF) might involve in the pathogenesis of mental disorders. There are inconsistent reports related to the role of BDNF Val66Met in susceptibility to bipolar disorder (BD).
The aim of the present study was to investigate the role of BDNF Val66Met and its synergism with 5-HTT gene-linked polymorphic region (5-HTTLPR) variants in susceptibility to bipolar I disorder (BP-I) in Western Iran.
In this case-control study, 153 patients with BP-I and 146 age- and gender-matched healthy individuals were investigated for BDNF and 5-HTTLPR variants using PCR-RFLP method.
The frequency of BDNF A (Met) allele in patients (17.7%) was slightly lower than that in controls (19.9%, P = 0.5). The concomitant presence of BDNF G (Val) and 5-HTTLPR S alleles tended to increase the risk of BP-I by 1.41 times (P = 0.064) compared to the combined presence of BDNF G and 5-HTTLPR L alleles. Also, interaction between BDNF G (Val) and 5-HTTLPR S tended to increase the risk of BP-I by 1.28-fold (P = 0.062) compared to the concomitant presence of BDNF A and 5-HTTLPR S alleles.
This study, conducted for the first time on Kurdish population in Western Iran, did not indicate any association between BDNF Val66Met with BP-I. However, the interaction between BDNF and 5-HTTLPR variants tended to increase the susceptibility to BP-I.

Multiple sclerosis (MS) is a common chronic genetic disease of the central nervous system. The relapsing-remitting-MS (RR-MS) is the most common form of this disease. Matrix metalloproteinase-7 (MMP-7) is an important member of the MMP family, which degrades many extracellular matrix components. The common polymorphism of MMP-7 A-181G is associated with some diseases. The aim of the present study was to determine the influence of this polymorphism on the risk of RR-MS. Eighty RR-MS patients and 80 healthy individuals as controls from the Kermanshah province were studied for MMP-7 A-181G polymorphism by using the PCR-RFLP method. Data were analyzed using the SPSS statistical software package version 16.0. In RR-MS patients the frequency of MMP-7 GG genotype was significantly (P = 0.028) higher compared to that of the controls. The presence of GG genotype increased the risk of RR-MS by 1.69 times [OR = 1.69 and 95% CI = 1.05- 2.72, P = 0.03]. The frequency of MMP-7 G allele in RR-MS patients was significantly higher (51.2%, P = 0.043) than that of the controls (40%). The presence of this allele increased the risk of RR-MS by 1.58 folds (P = 0.044). Our findings indicate that the presence of G allele of MMP-7 A-181G polymorphism might increase the risk of RR-MS in our population.

There are inconsistent reports related to the role of angiotensin II type 1 receptor (AT1R) on the risk of type 2 diabetes mellitus (T2DM) and its renal complications. To identify the association between AT1R A1166C variants with the risk of T2DM and also with diabetic nephropathy (DN). Patients and In a case-control study, the AT1R A1166C polymorphism was detected in 135 T2DM patients with and without DN and in 98 healthy subjects from Western Iran. The genotypes of AT1R A1166C polymorphism were detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The frequencies of AT1R A1166C genotypes and alleles were not significantly difference between patients with and without DN and controls. The frequencies of rare allele of 1166 C were 10%, 16.5%, 15.9% and 15.3% in micro-, macro- and normo-albuminuric patients and in healthy individuals, respectively (P > 0.05). The systolic blood pressure and serum creatinine level in DN patients were significantly higher in carriers of AT1R CC compared to carriers of AT1R AA genotype. In the presence of uncontrolled hyperglycemia (HbA1c > 7.5%), there was a trend toward increased risk of macro-albuminuria in carriers of AC+CC genotype (OR=3.66, [95% CI: 0.81-16.58], P = 0.092). Our study indicated the absence of an association between AT1R A1166C polymorphism with the risk of T2DM and DN. It seems in carriers of AT1R C allele systolic blood pressure and serum creatinine level to be higher compared to the A allele carriers.

Preeclampsia is a pregnancy complication with unknown etiology and its incidence is associated with genetic and environmental factors. There are inconsistent reports related to the role of endothelial nitric oxide synthase (eNOS) 4a/b polymorphism on the risk of preeclampsia development. The aim of the present study was to investigate the possible influence of eNOS 4a/b and its synergism with eNOS G894T polymorphism on the risk of preeclampsia. The present case-control study consisted of 179 unrelated women with preeclampsia including 118 with mild and 61 with severe preeclampsia and 96 unrelated women with normal pregnancy as controls. All studied women were from Kermanshah Province of Iran. eNOS 4a/b and G894T genotypes were detected using polymerase chain reaction (PCR), and PCR-restriction fragment length polymorphism (RFLP) methods, respectively. The categorical variables between groups were compared using χ2 test and the Odds ratios (OR) were obtained by SPSS logistic regression. Statistical significance was assumed at p<0.05 level. The frequency of eNOS a allele was slightly higher in both mild (16.5%) and severe (17.2%) preeclamptic women than controls (15.1%). Also, no significant difference was found between early- and late-onset preeclamptic women regarding the distribution of eNOS 4a/b genotypes. The presence of each allele of eNOS a or T was not associated with the risk of preeclampsia. However, the concomitant presence of both eNOS a and T alleles was associated with a non significant increased risk of severe preeclampsia by 1.77-fold (p=0.35). The present study indicates the lack of association between eNOS a and T alleles with the risk of mild preeclampsia and a non significant increased risk of severe preeclampsia in the presence of both alleles which needs to be investigated in a study with larger samples.

We conducted the present study to investigate the frequency of prothrombin G20210A mutation among acute lymphoblastic leukemia patients and healthy individuals from Western Iran and to detect the possible association between this mutation and the risk of acute lymphoblastic leukemia in our population. The studied groups consisted of 92 children with acute lymphoblastic leukemia and 249 age- and sex-matched healthy children from Western Iran. The prothrombin G20210A mutation was identified by PCR-RFLP using the restriction enzyme of Hind III. The prevalence of prothrombin 20210 GA genotype was 6.5% in patients and 3.2% in controls (P=0.17). The frequency of the A allele in patients was 3.3% and in controls it was1.6%. The present study indicates the absence of any significant differences in the frequency of the prothrombin G20210A mutation between acute lymphoblastic leukemia patients and healthy individuals. The results suggest that this mutation may not be a risk factor for acute lymphoblastic leukemia in our population.

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. The risk of thrombophilia increases in patients with ALL during chemotherapy. The present study aimed to investigate the frequency of factor V Leiden (FVL) mutation in children with acute lymphoblastic leukemia and its possible association with ALL.Patients and We studied 92 patients with ALL and 249 healthy individuals from Kermanshah Province of Iran. Detection of FVL mutation was performed by PCR-RFLP using restriction enzymes of Mnl I. The frequency of FVL G1691A polymorphism was 7.8% in patients compared to 3.2% in controls (p=0.052). There was a trend towards increased risk of ALL in the presence of FVL mutation [OR=2.54, 95% CI 0.9-7.2, p=0.08]. Our results indicated that the frequency of both thrombophilic mutation of FVL was higher in ALL patients from Kermanshah province compared to healthy individuals and FVL mutation tended to be associated with the increased risk of ALL. Further studies needed to evaluate the association between FVL mutation and the occurrence of thromboembolism in ALL patients.