Oxidative stress parameters and keap 1 variants in T2DM: Association with T2DM, diabetic neuropathy, diabetic retinopathy, and obesity.

INTRODUCTION: Chronic hyperglycemia activates the inflammatory pathways and oxidative stress mechanisms with consequent damage to nerve tissue and retina. The Keap1-Nrf2 pathway acts as one of the most important antioxidant pathways of the organism. Variants of Keap1 could affect susceptibility to diabetes and its complications. METHODS: In a case-control study, 400 individuals included type 2 diabetes mellitus (T2DM) patients without complication, with neuropathy, with retinopathy, and healthy individuals were investigated. The levels of glutathione (GSH), glutathione peroxidase (GPx), malondialdehyde (MDA), and total antioxidant capacity (TAC) were measured using chemical methods. Using the PCR-RFLP method, the Keap1 (rs11085735) variants were identified. RESULTS: Neuropathic patients had significantly lower levels of GSH, GPx, and TAC and higher levels of total oxidative status (TOS), MDA, and oxidative stress index (OSI) compared to T2DM patients without complication and controls. Lower levels of GSH and GPx and a higher level of MDA were observed in patients with retinopathy compared with controls. Obesity was associated with significantly lower GPx activity and higher TOS. A significantly higher Keap1 AA genotype was found in patients with neuropathy than T2DM without complication and controls. The presence of Keap1 AA genotype correlated with lower GPx activity compared to CC genotype. CONCLUSIONS: Our study suggests the role of reduced antioxidant system and Keap1 variants in the pathogenesis of T2DM and its complications of neuropathy and retinopathy and also obesity in enhanced oxidative stress. Monitoring oxidative stress parameters in diabetic patients, especially those with complication and their treatment with antioxidants is suggested.

Variants of Genes Involved in Metabolism of Folate Among Patients with Breast Cancer: Association of TYMS 3R Allele with Susceptibility to Breast Cancer and Metastasis.

BACKGROUND & OBJECTIVE: Breast cancer (BC) is known to be the most prevalent cancer among women. One-carbon metabolism 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. METHODS: The present case-control study includes 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. RESULTS: 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. CONCLUSION: We observed that the TYMS 3R is a risk allele for susceptibility to BC and this allele may increase the risk of metastasis in BC patients. .

p53 p.Pro72Arg (rs1042522) and Mouse Double Minute 2 (MDM2) Single-Nucleotide Polymorphism (SNP) 309 Variants and Their Interaction in Chronic Lymphocytic Leukemia(CLL): A Survey in CLL Patients from Western Iran.

Background: 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. Materials and Methods: 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. Results: 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. Conclusion: 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.

Gene variants and haplotypes of Vitamin D biosynthesis, transport, and function in preeclampsia.

Objective: To find whether the gene variants and haplotypes of cytochrome (CYP) 27B1 (1α-hydroxylase), group-specific component (GC) that is a vitamin D binding protein, vitamin D receptor (VDR), peroxisome proliferator-activated receptor γ (PPARγ) and retinoid-X receptor (RXR) affect the risk of preeclampsia. Methods: In a case-control study 100 women with preeclampsia and 100 healthy pregnant women were investigated for gene variants and haplotypes of vitamin D biosynthesis, transport, and function using the polymerase chain reaction-restriction fragment length polymorphism method. Results: The frequency of gene variants of PPARγ Pro12Ala and RXR -α (A/G, rs749759) were not significantly different comparing patients and controls. The TT genotype of CYP 27B1 (G > T) was associated with 2.2-fold (95% CI 1.04-4.7, p = 0.039) increased risk of early-onset preeclampsia. Also, the TT genotype of GC rs7041 (T > G) increased the risk of preeclampsia [OR = 2.13 (95% CI 1.09-4.17, p = 0.027)]. The VDR ApaI GT genotype elevated susceptibility to preeclampsia (OR = 2.55, p = 0.04). Further, the presence of VDR ApaI GT+TT genotype was associated with higher levels of body mass index, and systolic blood pressure, and lower level of 25 (OH)-D3. In the presence of haplotype CYP T, VDR T, and RXR A (TTA) compared to haplotype GTG the risk of preeclampsia was 6.71-fold (p = 0.044). Conclusions: The present study indicated an association between the CYP 27B1, GC, and VDR ApaI variants with the risk of preeclampsia. Also, the variants of the latter polymorphism influenced BMI, blood pressure, and vitamin D levels.

The Insulin-like Growth Factor-1 (G>A) and 5,10-methylenetetrahydrofolate Reductase (C677T) Gene Variants and the Serum Levels of Insulin-like Growth Factor-1, Insulin, and Homeostasis Model Assessment in Patients with Acne Vulgaris.

BACKGROUND & OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

NOTCH1, SF3B1, MDM2 and MYD88 mutations in patients with chronic lymphocytic leukemia.

Mutations in certain genes have been suggested to be associated with the pathogenesis of chronic lymphocytic leukemia (CLL), which is the most common leukemia in adults. In a case-control study, 100 patients with CLL and 105 healthy individuals were investigated for Notch homolog 1, translocation-associated (Drosophila) (NOTCH1) c.7544-7545delCT, recombinant splicing factor 3B subunit 1 (SF3B1) c.2098A>G, mouse double minute 2 homolog (MDM2) 40-bp insertion/deletion and myeloid differentiation primary response 88 (MYD88) L265P mutations by using allele specific-polymerase chain reaction (AS-PCR), a designed AS-PCR, PCR and PCR-restriction fragment length polymorphism methods, respectively. The presence of NOTCH1 and SF3B1 mutations were confirmed by genomic DNA sequencing. The NOTCH1 mutation was detected in 10% of patients and not detected in the control group. A higher frequency of NOTCH1 mutation was detected in patients with stage III CLL (62.5%) compared with stages 0-II CLL (37.5%) (odds ratio, 4.69-fold; 95% confidence interval, 1.0-21.9; P=0.049). The SF3B1 mutation was observed in 12% of the patients compared with 1.9% of the controls (P=0.012). The presence of MDM2 polymorphism was not associated with the risk or the stage of the disease. In addition, the MYD88 L265P mutation was not detected in the patients or the controls. The current study established the frequency of NOTCH1, SF3B1, MDM2 and MYD88 mutations in patients with CLL from the Kurdish population of Western Iran. In summary, a high frequency of NOTCH1 and SF3B1 mutations were identified in patients with CLL compared with healthy individuals, and the NOTCH1 mutation was associated with a high stage of the disease.

Association between CYP19A

Acne vulgaris (AV) is a common skin disease that causes physical and psychological problems for the 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 effect of VDR gene polymorphisms and vitamin D level on blood pressure, risk of preeclampsia, gestational age, and body mass index.

We investigated the influence of vitamin D receptor (VDR) polymorphisms and vitamin D level on the blood pressure and the risk of preeclampsia. In a case-control study, 200 pregnant women, including 100 individuals with preeclampsia along with 100 healthy pregnant women, were studied for VDR FokI, TaqI, and BmsI polymorphisms and serum 25 (OH)-D level using polymerase chain reaction-restriction fragment length polymorphism method and commercial kit, respectively. The mean level of 25 (OH)-D in preeclamptic patients was significantly lower (16.6 ± 4.2 ng/mL, P < 0.001) compared with controls (19.6 ± 3.8 ng/mL). Among all women, a significantly higher systolic blood pressure and before-pregnancy body mass index and also lower gestational age were observed in the presence of 25 (OH)-D level < 20 ng/mL compared with the 20 to 30 ng/mL. A significantly higher frequency of VDR FokI C allele in preeclamptic patients (83%) than controls (74%) was associated with a 1.72-fold increased risk of preeclampsia. In all the studied individuals, the systolic and diastolic blood pressures were significantly higher in the presence of the FokI CC genotype compared with the TC and TT+TC genotypes. Neither VDR Taq1 nor VDR BmsI was associated with the risk of preeclampsia. The haplotype FokI C, TaqI C and BmsI A (CCA) compared with haplotype CTG increased the risk of preeclampsia by 1.4-fold (P = 0.33). Our study suggests an association between VDR FokI polymorphism and an insufficient serum level of 25 (OH)-D with the risk of preeclampsia and also the influence of insufficient 25 (OH)-D level and VDR FokI polymorphism on maternal factors, including blood pressure.

The Association of PPARγ Pro12Ala and C161T Polymorphisms with Polycystic Ovary Syndrome and Their Influence on Lipid and Lipoprotein Profiles.

BACKGROUND: 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. MATERIALS AND METHODS: 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 genotyped 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 lipoproteincholesterol (HDL-C) and estradiol levels were measured. RESULTS: 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 genotype 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. CONCLUSION: 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.

PPARγ Pro12Ala and C161T polymorphisms in patients with acne vulgaris: Contribution to lipid and lipoprotein profile.

PURPOSE: The aim of present study was to clarify the role of peroxisome proliferator-activated receptor γ (PPARγ) Pro12Ala and C161T variants in the pathogenesis of acne vulgaris (AV) and their influence on lipid and lipoprotein profile. METHODS: The present case-control study consisted of 393 individuals including 198 patients with AV (mild-, moderate-, and severe-AV) and 195 unrelated age-matched healthy individuals from Western Iran. The PPARγ Pro12Ala and C161T polymorphisms were identified using polymerase chain reaction-restriction length polymorphism method. Also, serum lipid and lipoprotein profile and fasting blood sugar (FBS) were detected in studied individuals. RESULTS: In women patients with AV significantly higher serum levels of FBS, total cholesterol, low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein-cholesterol compared to healthy women were detected. Neither PPARγ Pro12Ala nor C161T polymorphism was associated with the risk of AV but the Pro allele was a risk factor for AV among all men and women patients ≥20years. The variant genotype of PPARγ CG (Pro/Ala) was associated with significantly higher levels of total cholesterol and triglycerides compared to CC (Pro/Pro) genotype. We detected a significantly lower level of FBS in the presence of CT+TT genotype of PPARγ C161T compared to CC genotype. Also, carriers of PPARγ TT genotype had significantly lower serum level of total cholesterol and LDL-C compared to CC genotype. CONCLUSIONS: Our results demonstrated the association of PPARγ Pro allele with susceptibility to AV in patients ≥20years and the influence of PPARγ Pro12Ala and C161T polymorphisms on the lipid and lipoprotein profile.

MMP-8 C-799T and MMP-8 C+17G polymorphisms in mild and severe preeclampsia: Association between MMP-8 C-799T with susceptibility to severe preeclampsia.

OBJECTIVE: The aim of present study was to determine the role of matrix metalloproteinase-8 (MMP-8) C-799T (rs11225395) and C+17 (rs2155052) polymorphisms in susceptibility to preeclampsia. STUDY DESIGN: In a case-control study, 256 pregnant women including 152 women with preeclampsia (86 women with mild preeclampsia and 66 women with severe preeclampsia) and 104 women with normal pregnancy from Western Iran with Kurdish ethnic background were investigated for MMP-8 C-799T and C + 17G polymorphisms using polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: Comparing the MMP-8 TT genotype with the combined genotype of CC+CT (recessive model) indicated a significantly higher frequency of the MMP-8 TT genotype (47%) in severe preeclamptic patients than that in healthy pregnant women (30.8%) that was associated with 1.99-fold increased risk of severe preeclampsia (95% CI = 1.05-3.77, p = 0.034). The frequency of MMP-8 G allele was 27.3% in all preeclamptic patients compared to 30.2% in controls (p = 0.56). Also, no significant difference was detected comparing the frequency of G allele in mild (26.6%, p = 0.46) and severe preeclamptic patients (28.4%, p = 0.75) with controls (30.2%). CONCLUSIONS: Our study demonstrated that the MMP-8 C-799T is associated with the risk of developing severe preeclampsia during pregnancy. However, the MMP-8 C + 17G polymorphism might not be a risk factor for susceptibility to preeclampsia.

Matrix metalloproteinase-2 C-735T and its interaction with matrix metalloproteinase-7 A-181G polymorphism are associated with the risk of preeclampsia: influence on total antioxidant capacity and blood pressure.

Matrix metalloproteinase (MMP) -2 C-735 T and MMP-7 A-181 G genotypes were studied in 144 pregnant patients with mild and severe preeclampsia and 103 healthy pregnant women. Significantly higher frequencies of CT and TT genotypes in patients compared to controls increased the risk of preeclampsia by 2.42 and 3.13 times, respectively. In severe preeclamptic women in the presence of MMP-2 CT the level of total antioxidant capacity was significantly lower than MMP-2 CC genotype. Also, in the presence of MMP-2 CT + TT blood pressure was significantly increased compared to CC genotype in all the patients. The combined presence of MMP-2 T and the MMP-7 A alleles compared to MMP-2 C and MMP-7 A alleles significantly increased the risk of preeclampsia by 3.08-fold. Our findings demonstrate an association between the MMP-2 C-735 T polymorphism with blood pressure and the risk of preeclampsia. Also, in the presence of polymorphism total antioxidant capacity level decreased in severe preeclampsia. Impact statement What is already known on this subject: Matrix metalloproteinases (MMPs) including MMP-2 might be involved in the pathogenesis of preeclampsia through alteration of invasive ability of trophoblastic cells and abnormal placentation. In one available study the absence of association between MMP-2 C-735T polymorphism with gestational hypertension or preeclampsia has been reported. What the results of this study add: We found that the presence of MMP-2 C-735T polymorphism increased the risk of preeclampsia and there was a significantly lower level of total antioxidant capacity in the presence of the polymorphism in severe preeclampsia. Also, we found significantly higher systolic and diastolic blood pressures in the presence of MMP-2 C-735T polymorphism. We detected a synergism between the MMP-2 T and the MMP-7 A alleles that increased the risk of preeclampsia. What the implications are of these findings for clinical practice and/or further research: New findings of our study are involvement of lower activity MMP-2 -735 T allele and its synergism with MMP-7 A allele, low promoter activity allele, in the pathogenesis of preeclampsia through possible impairment of placentation and also by decreased total antioxidant capacity and increased blood pressure. Further association studies of the role of MMP-2 polymorphism and MMP-2 activity in relation to oxidative stress parameters and blood pressure could elucidate the role of MMP-2 and MMP-7 in the pathogenesis of preeclampsia.

ACE I/D and MMP-7 A-181G variants and the risk of end stage renal disease.

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.

Functional Promoter Polymorphisms of MMP-2 C-735T and MMP-9 C-1562T and Their Synergism with MMP-7 A-181G in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system. Matrix metalloproteinases (MMPs) play an important role in breakdown of blood-brain barrier, transmigration, and invasion of immune cells and formation of MS lesions. The aim of present study was to investigate the influence of MMP-2 C-735T and MMP-9 C-1562T variants and their synergism with MMP-7 A-181G on susceptibility to MS. In a case-control study 125 MS patients and 235 healthy individuals from Western Iran were investigated. The various genotypes of MMP-2, MMP-9, and MMP-7 were detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In females the presence of MMP-2 C allele was associated with an increased risk of MS (OR = 1.69, p = 0.041). No significant difference was detected between the frequency of MMP-9 T allele in MS patients (8.2%) and controls (12.8%, p = 0.068). The concomitant presence of both MMP-2 C and MMP-7 G alleles was associated with 1.82-fold increased risk of MS (p = 0.002). Also, a synergism was detected between MMP-9 C and MMP-7 G alleles that elevated the risk of MS by 1.5-times (p = 0.035). The presence of haplotype MMP-9 T, MMP-7 G, and MMP-2 C (TGC) compared to haplotype CAG increased the risk of MS by 3.13-fold (p = 0.16). The present study suggests that gene-gene interactions and variants of more genes instead of single gene might play a role in susceptibility to MS. We indicated that synergism between variants of MMP-2, MMP-7, and MMP-9 genes might increase the risk of MS.

The T Allele of MTHFR c.C677T and Its Synergism with G (Val 158) Allele of COMT c.G472A Polymorphism Are Associated with the Risk of Bipolar I Disorder.

AIMS: The aims of the present study were to investigate the association between methylenetetrahydrofolate reductase (MTHFR) c.C677T (p.A222V) and catechol-O-methyltransferase (COMT) c.G472A (p.V158M) polymorphisms and their synergism with respect to bipolar I disorder (BID). METHODS: Within an ethnic Kurdish population from Western Iran the MTHFR c.C677T and COMT c.G472A polymorphisms were studied in 150 patients with BID and 149 gender- and age-matched healthy individuals using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: In the presence of MTHFR 677T allele and MTHFR TT genotype, the risk of BID was 1.44 times (p = 0.046) and 1.81-fold (p = 0.029), respectively. The frequency of COMT 472G allele compared to the A allele in cases and controls was not significant (p = 0.078); however there was a synergism between the presence of MTHFR 677T and COMT 472G alleles that increased the risk of BID by 2.58-fold (p = 0.003). CONCLUSIONS: Our findings indicate that the presence of the lower activity allele of MTHFR (677T) increased the risk of BID. In addition, the concomitant presence of the MTHFR 677T allele with the COMT 472G allele was associated with increased susceptibility to BID in our population.

AT1R A1166C variants in patients with type 2 diabetes mellitus and diabetic nephropathy.

BACKGROUND: 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. OBJECTIVES: To identify the association between AT1R A1166C variants with the risk of T2DM and also with diabetic nephropathy (DN). PATIENTS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Matrix metalloproteinase-9 -1562T allele and its combination with MMP-2 -735 C allele are risk factors for breast cancer.

BACKGROUND: Expression of matrix metalloproteinases (MMPs) is up-regulated in human cancers. The aim of present study was to investigate the role of MMP-9 C-1562T polymorphism and its interaction with MMP- 2 C-735T polymorphism in susceptibility to breast cancer in a population from Western Iran with Kurdish ethnic background. MATERIALS AND METHODS: The study sample of 205 individuals consisted of 101 breast cancer patients and 104 healthy subjects. MMP-9 C-1562T and MMP-2 C-735T variants were identified using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: Among 67.4% of studied patients the breast cancer developed in the third and forth decades of the life. The frequency of MMP-9 T allele was 17.3% in patients and 10.1% in controls. The presence of T allele significantly increased the risk of breast cancer by 1.87-fold [OR=1.87 (95% CI 1.05-3.33, p=0.035)]. The frequency of MMP-9 CT+TT genotype tended to be higher in those patients with a family history of cancer in first degree-relatives (36.8%) than those without a family history (28.3%, p=0.37). We observed an interaction between the MMP-9 -1562 T allele with MMP-2 -735 C allele that significantly increased the risk of breast cancer [OR=1.42 (95% CI 1.02- 1.98, p=0.036)]. CONCLUSIONS: The present study demonstrated that MMP-9 C-1562T polymorphism alone and in combination with MMP-2 C-735T polymorphism increased the risk of breast cancer that might be a useful biomarker in identifying women at risk of developing breast cancer. Also, this study revealed that in most women from Western Iran breast cancer presents in third and fourth decades of life.

Cancer notification at a referral hospital of Kermanshah, Western Iran (2006-2009).

BACKGROUND: Cancer is a major public health problem and the leading cause of mortality in both males and females in developed and developing countries. The incidence of cancer is gender dependent. Among Iranians, it is the third cause of death. MATERIALS AND METHODS: The information recorded in the files of all patients (7,695 individuals) pathologically diagnosed with cancer in Imam Reza referral hospital of Kermanshah University of Medical Sciences during the four year period of 2006-2009 were reviewed and analyzed using SPSS statistical software package version 16.0. RESULTS: Around 61.6% of reported cancer cases were males and 38.4% were females. The most prevalent reported malignant tumors occurred at the age group of 70-79 years in males and in females these tumors were presented in the ages of 60-69 years. The most prevalent cancers among studied patients were gastrointestinal (GI) cancers with a frequency of 22.9% [gastric 10.7%, colorectal 6.9%, and esophageal 6%]. The second, third and forth prevalent cancers were blood at 16.4%, lung 13.5% and bladder 12.8%, respectively. In males the cancers of GI (25.6%) were the most prevalent followed in order of frequency by bladder (18%), blood (17.6%), lung (17.4%) and prostate (6.8%) . In females the most frequent recorded cancer was breast (24.1%) followed in order of frequency by GI (20.5%), blood (14.4%), lung (7.3%), uterus (6.2%) and ovary (5.1%) . Breast cancer was the most prevalent cancer (27%) in the age group of 40-49 years. CONCLUSIONS: The present study provides frequency data for various types of cancers in both males and females from a referral hospital of Kermanshah that are comparable with some reports from other areas of the country.

The serotonin transporter (5-HTTLPR) but not serotonin receptor (5-HT2C Cys23Ser) variant is associated with bipolar I disorder in Kurdish population from Western Iran.

The role of 5-HTTLPR and 5-HT2C Cys23Ser polymorphisms in the psychopathology of mood disorders and suicide behavior is controversial. The aim of present study was to investigate the association between 5-HTTLPR and 5-HT2C Cys23Ser variants and susceptibility to bipolar I disorder (BID). The 5-HT2C genotypes were studied in 152 patients with BID and 173 gender- and age-matched healthy individuals with Kurds ethnic background from Western Iran using PCR and PCR-RFLP methods. In recessive model (SS vs. LL+LS) the SS genotype was associated with 1.79-fold increased risk of BID (p=0.018). Also, the presence of S allele increased the risk of adult-onset BID by 1.76-fold (p=0.027). No association was detected between 5-HTTLPR genotypes and alleles with suicide attempt. The frequency of 5-HT2C Ser allele in patients and controls were 12.3 and 12.5%, respectively. Mutant allele of HT2C Ser had higher frequency in female (14.7%) than male (10.5%, p=0.27) patients. The frequency of HT2C Ser allele in patients with a family history of BID tended to be higher (15.7%) than those without a family history of the disease (11.8%). The frequency of HT2C Ser allele in suicide attempter women was higher (16.7%) than those without a suicide attempt (14.3%). Our findings demonstrate 5-HTTLPR polymorphism might be a risk factor for BID and adult-onset BID in Kurds population. However, we found the lack of an association between 5-HT2C Cys/Ser variants and the risk of BID.