Gene Promoter Polymorphism Research Articles

MMP-2 and MMP-9 gene polymorphisms and risk of head and neck carcinomas

Abstract Background: Head and neck carcinomas (HNC) account for a majority of ear, nose and throat tumours. They account for 6.3% of all incident malignancies and 6.2 % of all deaths from cancer in Romania in 2020, the fifth most common cancer in this Eastern Europe country. Aim of the study: The aim of our study was to investigate the association between two MMP-2 and MMP-9 promoter gene polymorphisms and head and neck cancer. Methods. We enrolled 142 subjects, 65 cancer patients, and 77 control subjects and tested them for MMP-2 -735 C/T and MMP-9 -1562 C/T polymorphisms by PCR-RFLP. Results. Comparison between cancer patients and controls demonstrated the presence of MMP-2 -735 C/T and MMP-9 -1562 C/T in head and neck malignant tumours, with OR = 2.206 (95% CI 1.058-4.599, P = 0.03) for MMP-2 and OR = 2.748 (95% C.I. 1.262-5.981, P=0.009) for MMP-9 gene polymorphism. This means that the presence of T allele could be a risk factor for head and neck cancer development. The analysis included a stratification of studied groups by age and gender. Conclusions. Both genotypes were associated with a significant risk for head and neck carcinomas in case of the presence of the T allele. MMP-2 -735 C/T (rs2285053) and MMP-9 -1562 C/T (rs3918242) gene polymorphism could be an important genetic marker for head and neck cancer susceptibility. This finding could be useful for genetic screening in head and neck carcinomas.

Lack of association between CYP27B1 gene polymorphism and type 2 diabetes mellitus in Iranian patients.

Type 2 diabetes mellitus (T2DM) is a global health problem with multiple etiological factors. Previous studies indicated that 1- alpha, 25-dihydroxyvitamin D3, a molecule that is produced by CYP27B1, could protect insulin-secreted cells from destruction by immune cells. The aim of the study was to investigate the CYP27B1 promoter gene polymorphism in T2DM. Two hundred subjects including 100 T2DM and 100 healthy individuals were recruited in the study. ARMS-PCR technique was used to identify rs10877012 genotypes in the 5' region of CYP27B1. The frequency of CC, CA, and AA genotype was 61/50, 31/39, and 8/11, respectively in T2DM patients compared to healthy subjects. There was no significant difference between both groups in regarding to genotype and allele distribution (P > 0.05). CA (RR = 1.535, 95% CI = 0.841- 2.802) and AA (1.677, 95% CI = 0.627-4.490) genotypes had no association with increased risk of T2DM. In addition, CA + AA versus CC showed no increased risk for T2DM (RR = 0.639, 95% CI = 0.365-1.121). We found no association between rs10877012 polymorphism and T2DM. There was no increased risk of this polymorphism in T2DM. Further studies with large groups are suggested in other populations to better understand the relation of CYP27B1 gene variation, especially its ethnicity-dependent relation with T2DM.

The Role Of “Il 10 (-2 1082 A/G)” Promoter Polymorphism In Ovarian Epithelial Cancer Pathogenesis

Ovarian cancer (ovarian cancer) is the abnormal development of cells in one or two ovaries. Many cytokine functions are related to the development of immunological and inflammatory responses that play essential roles in cancer pathogenesis. Among the cytokines, interleukin 10 (IL-10) is an anti-inflammatory cytokine involved in the downregulation of cytotoxic and inflammatory cell-mediated responses. This study aims to determine the relationship between the Gene Promoter Polymorphism Interleukin 10 (-1082 A/G) with the incidence of ovarian epithelial cancer. This research is an observational analytical study conducted at the Molecular Biology Laboratory in Palembang City in October-December 2021. The number of samples was 60 respondents consisting of 30 case groups and 30 control groups. Data were obtained by genotype and allele using PCR-RFLP, which was then analyzed by Chi-Square test to determine whether there was a relationship. The results showed no significant relationship between the promoter of the IL 10 gene polymorphism (-1082 A/G) and the incidence of ovarian epithelial cancer.

Macrophage migration inhibitory factor gene promoter polymorphism (−173G/C SNP) determines host susceptibility and severity of leptospirosis

The biological mechanisms that are associated with the severity of leptospirosis are far from complete. The aim of the present study was to investigate whether the macrophage migration inhibitory factor (MIF) gene promoter polymorphisms determine susceptibility to and severity of human leptospirosis. MIF is a potent pro-inflammatory cytokine, which has been reported to correlate with the risk of inflammatory disease onset and severity. In the present study, MIF 173G/C single nucleotide polymorphism (SNP) was analyzed by PCR-RFLP (Restriction fragment length polymorphism). A statistically significant increase of MIF -173*C allele related genotypes was observed in leptospirosis patients when compared with healthy control subjects. Genotypes GC (OR: 28.4; 95% CI: 10.9–73.6; p < 0.001) and CC (OR: 40; 95% CI: 2.3–686.5; p < 0.001) of −173 G/C MIF polymorphism was associated with susceptibility and severity of leptospirosis respectively. In leptospirosis cases, 69.8% of leptospirosis patients were GC genotype carriers while 19.8% and 10.4% cases were CC and GG carriers; in severe leptospirosis, 68% cases were CC carriers and 32% were GC carriers; and in healthy controls, 92.5% subjects were GG carriers and 7.5% were GC carriers. MIF -173*C allele was (OR: 15; 95% CI: 6.1–36.8; p < 0.001) significantly associated with the risk of leptospirosis than −173*G allele (OR: 0.06; 95% CI: 0.02–0.16; p < 0.001). The relationship of −173G/C MIF polymorphism with mRNA and serum level of MIF and inflammatory cytokine expression was analyzed by quantitative real-time PCR and MIF ELISA. MIF mRNA expression was significantly increased in carriers of MIF -173*C allele associated genotypes, GC and CC. A substantial increase of serum MIF (Mean ± SD) was found in risk genotypes GC (5.81 ± 0.61 ng/mL) and CC (10.12 ± 0.23 ng/mL) carrying leptospirosis patients than GG genotype (0.86 ± 0.3 ng/mL) carrying healthy controls. Pearson correlation test showed a significant positive correlation between elevated serum MIF and −173*C allele (r = 0.99, p < 0.001). High MIF expression genotypes GC and CC upregulated the mRNA expression of TNF-α, IL-1β and IL-4 whereas downregulated the IL-10 expression. Thus, MIF -173 G/C SNP genotype GC carriers have highly susceptible to leptospirosis and the leptospirosis patients with CC genotype had an increased risk of developing a severe form of the disease. The observations of this study conclude that MIF -173G/C polymorphism is associated with leptospirosis susceptibility and severity and also could be a promising severity predictor of leptospirosis.

Interleukin 32 gene promoter polymorphism: A genetic risk factor for multiple sclerosis in Kashmiri population

ObjectiveAlthough the exact cause of multiple sclerosis is not known, there are a number of factors involved mainly environmental and genetic factors. The present study was done to determine association between IL-32 gene promoter polymorphism and IL-32 levels with multiple sclerosis. Methods48 relapsing remitting multiple sclerosis patients and 60 healthy controls were compared for IL-32 gene promoter polymorphism and IL-32 levels. ResultsThere was no significant difference in genotype CT between the MS patients and healthy controls (p 0.130) where as a significant difference in genotype (CC) frequencies among MS patients and healthy controls (p 0.039) was observed. The difference in C allele frequency was also statistically significant between two study groups (p 0.01). Multivariate regression analysis revealed that the CC genotype might impact the risk of disease susceptibility up to 3.71 times and the presence of C allele might increase the risk of susceptibility to multiple sclerosis by 2.26 fold. The serum IL-32 levels were not statistically different multiple sclerosis patients and healthy controls and between wild and mutant genotypes. ConclusionsIL-32 gene promoter polymorphism is a genetic risk factor for multiple sclerosis patients particularly women.

Tumor Necrosis Factor-α-863C/A and 1031 T/C Single nucleotide polymorphic sites (SNPs) may be putative markers of HBV disease prognosis among Caucasoids: Evidence from a systematic review with meta-analysis

BackgroundThe pathogenesis and prognosis of hepatitis B virus (HBV) infection have been correlated with genetic polymorphisms in the gene loci within the promoter region of the immune system modulator molecules such as the cytokines including the tumor necrosis factor (TNF)-alpha. Besides, these polymorphisms vary at population levels but it is not conclusive whether races are involved or not. We aimed at testing the hypothesis that the SNPs in the promoter region of the TNF-alpha gene may have different effects in the Caucasoid populations by pooling the odds of association with the clearance/increased risk of the HBV infection from a large sample size obtained from many primary studies. We searched Scopus, PubMed, EMBASE, Cochrane, Willy and Google scholar databases for the published studies between January 1998 to December 2020. Studies that investigated the association between the TNF-α-238G/A, -308G/A, -857C/T, -863C/A and -1031 T/C gene promoter polymorphisms with the resolution/increased risk of HBV infection published in English and in peer reviewed journals were included. The odds ratios were used to evaluate the association of the TNF-α-gene SNPs with the risk/resolution of the disease. This study is registered on PROSPERO, number CRD42021266944. ResultsA significant association was observed between the TNF-α-857 homozygous mutation TT and its allele T with reduced risk of infection or resolution of the disease among both the Caucasoids and the Mongoloids (p < 0.05, OR < 1.0). In contrast, the TNF-α-1031 wild type genotypes TT; p = 0.001, OR = 0.634, 95%CI = [0.489 to 0.822%] and its allele T; p = 0.001, OR = 0.701, 95%CI = [0.571 to 0.860%] were significantly associated with reduced risk of infection or increased chances of resolution of the disease among the Caucasoids only. However, the TNF-α-863 homozygous mutation AA or its allele A and the TNF-α-1031 heterozygous mutation CT or the allele C were significantly associated with unresolved HBV infection among the Caucasoids (p < 0.05, OR > 1.0) but not among the Mongoloids. ConclusionTumor Necrosis Factor-α-863C/A and 1031 T/C polymorphic sites may be putative markers of HBV disease prognosis and pathogenesis among the Caucasoid populations but not among the Mongoloid populations. Future research therefore should focus on the role of these presumed TNF-α-polymorphisms in the clinical profile of the HBV infections targeting an African or Negroid population.

A Thrombomodulin Promoter Gene Polymorphism, rs2239562, Influences Both Susceptibility to and Outcome of Sepsis.

Objective: Disseminated intravascular coagulation plays a key role in the pathophysiology of sepsis. Thrombomodulin is essential in the protein C system of coagulation cascade, and functional polymorphisms influence the human thrombomodulin gene (THBD). Therefore, we conducted a multicenter study to evaluate the influence of such polymorphisms on the pathophysiology of sepsis.Methods: A collaborative case-control study in the intensive care unit (ICU) of each of five tertiary emergency centers. The study included 259 patients (of whom 125 displayed severe sepsis), who were admitted to the ICU of Chiba University Hospital, Chiba, Japan between October 2001 and September 2008 (discovery cohort) and 793 patients (of whom 271 patients displayed severe sepsis), who were admitted to the five ICUs between October 2008 and September 2012 (multicenter validation cohort). To assess the susceptibility to severe sepsis, we further selected 222 critically ill patients from the validation cohort matched for age, gender, morbidity, and severity with the patients with severe sepsis, but without any evidence of sepsis.Results: We examined whether the eight THBD single nucleotide polymorphisms (SNPs) were associated with susceptibility to and/or mortality of sepsis. Higher mortality on severe sepsis in the discovery and combined cohorts was significantly associated with the CC genotype in a THBD promoter SNP (−1920*C/G; rs2239562) [odds ratio [OR] 2.709 (1.067–6.877), P = 0.033 and OR 1.768 (1.060–2.949), P = 0.028]. Furthermore, rs2239562 SNP was associated with susceptibility to severe sepsis [OR 1.593 (1.086–2.338), P = 0.017].Conclusions: The data demonstrate that rs2239562, the THBD promoter SNP influences both the outcome and susceptibility to severe sepsis.

Association of interleukin-17A gene promoter polymorphism with the susceptibility to generalized chronic periodontitis in an Iranian population

Chronic periodontitis (CP) is characterized by an immune response, leading to the destruction of periodontal supporting tissue. The effect of inflammatory and genetic factors on periodontitis has been evaluated previously. The interleukin (IL-17) as an inflammation regulator seems to play a critical role in periodontitis pathogenesis. Here, in the current study, we aimed to investigate the association of -197 G > A (rs2275913) IL-17 gene promoter polymorphism with generalized severe CP in an Iranian population. In this case-control study, a total of 54 patients with periodontitis and 118 normals were enrolled. The polymerase chain reaction-restriction fragment length polymorphism technique was applied to detect IL-17 promoter rs2275913 genotypes in association with the susceptibility to severe CP. Chi-square test or Fisher's exact test was employed to compare genotype frequencies between groups. P < 0.05 were considered statistically significant. The distribution of genotypes and alleles was in Hardy-Weinberg equilibrium. Although no significant association was observed between the risk of periodontitis and genotype frequencies under any of the inheritance models, the GG genotype was higher in healthy controls, while the AG genotype was more frequently observed in patients under the codominant model ([odd ratio [OR] = 2.14, 95% confidence interval (CI) (1.01-4.53), P = 0.13]). The frequency of AG-AA genotype was higher in patients under dominant inheritance model ([OR = 1.92, 95% CI (0.94-3.93), P = 0.068]), while GG-AA and AG genotypes were higher in healthy controls under over dominant model (OR = 0.1.95, 95% CI [0.98-3.86], P = 0.055). The results of this study showed that the presence of allele A and AG genotypes could be considered possible factors in increasing the risk of developing CP, although the differences of allele and genotype frequencies were remarkable but not statistically significant between the two groups.

Matrix metalloproteinase-9-1562 C/T promoter gene polymorphism in chronic periodontitis: A cross-sectional observational study.

Background:Matrix metalloproteinases (MMPs) are a major group of enzymes, released in inflamed periodontal tissues in large quantities, resulting in connective tissue matrix breakdown. One of the most predominant MMPs is MMP-9. Association between chronic periodontitis (CP) and MMP-9 gene polymorphism (GP) in some ethnic populations has been already established. The aim of the current study was to assess the association of single-nucleotide polymorphism in the promoter region of MMP-9 gene with CP in Kolkata population, if any.Materials and Methods:Forty eligible individuals were recruited for the study and grouped as A and B: Group A (twenty periodontally healthy individuals) and Group B (twenty CP patients). Venous blood samples collected from all the forty individuals were used to isolate the genomic DNA. GP for MMP-9 gene was detected using polymerase chain reaction and sequencing method. The data obtained were then analyzed statistically.Results:A significantly different genotypic and allelic variation was observed in the control and test groups, with C/T genotype and T allele present in only CP group.Conclusion:Within the limitations of this study, we can conclude that there was no significant association between patients with periodontitis and MMP-9-1562 C/T promoter GP.

Risk-taking in traffic is associated with unhealthy lifestyle: Contribution of aggressiveness and the serotonin transporter genotype

ObjectivesRisk taking behaviour, including in traffic, is related to impulsivity and aggressiveness, and so is unhealthy lifestyle. The serotonin transporter gene promoter polymorphism (5-HTTLPR) has been associated with impulsivity, aggression, alcohol use, speed limit exceeding and traffic accidents. The aim of this study was to examine whether subjects with less healthy eating and exercise habits take more risks in traffic, and whether impulsivity, aggressiveness and the serotonin transporter genotype could mediate or moderate any such associations. MethodA sub-sample of the Estonian Psychobiological Study of Traffic Behaviour (EPSTB (n ​= ​817) with mean age (SD) ​= ​31.4 (10.0) years filled out lifestyle questionnaires. Impulsivity was measured by Adaptive and Maladaptive Impulsivity Scale and aggressiveness by Buss – Perry Aggression Questionnaire. Traffic violation data in the previous 5 years period were obtained from police database. ResultsSpeed limit exceeders had higher physical and verbal aggression, higher AUDIT scores, they reported more vigorous physical activity and drinking energy drinks more often. Path analysis showed that higher AUDIT scores were associated with speeding via higher physical aggression. 5-HTTLPR was not directly associated with speeding or driving while impaired by alcohol (DWI), but 5-HTTLPR s’-allele carriers had lower AUDIT scores if they were not junk food eaters and the other way around, while l’/l’ homozygosity was associated with DWI via higher AUDIT scores. ConclusionSignificant associations exist between risky traffic behaviour and aspects of lifestyle such as consumption of alcohol or junk food or energy drinks, as well as engagement in vigorous physical activity, while traits such as aggressiveness and the variation in the serotonergic system appear as mediating and moderating factors. Interventions preventing accidents should focus on wider array of behaviours and use personalized approach. Genetic variation should be investigated regarding associations with risk taking and health behaviour, and response to interventions.

IDENTIFICATION OF MONOAMINOXIDASE-A GENE PROMOTER POLYMORPHISM (MAOA-UVNTR) AND THEIR RELATIONSHIP WITH AGGRESSIVE BEHAVIOR IN UKRAINIAN CHILDREN.

to investigate the interactive effect of monoamine oxidase-A gene promoter polymorphism (MAOA-uVNTR) and environmental factors on the development of aggressive behavior. Genotyping of the MAOA-uVNTR polymorphism was performed in 144 boys and girls aged from 10 to 16 years, genotypes were grouped by a high and low transcriptional activity. For the general assessment of the psycho-emotional sphere of children, the projective method «non-existent animal» was used, the indicators and forms of aggression were determined according to the method of A. Bass and A. Darky. It was found the predominant allelic variants of the MAOA gene with 3 (S) and 4 (L) tandem repeats. The presence of close relationships between the dependent variable «aggressive behavior» and the predictor variables: «family disadvantage index» and «MAOA-uVNTR genotype» was established. It has been proven that the presence of the highly active allele (L) in the genotype reduces the chances of developing general aggression, delinquent behavior, physical aggression, open aggression, negativism, and externalization. The MAOA genotype of the high-activity allele (L) moderated the impact of stressful life events, and the low-activity allele S was associated with increased aggression in girls and boys who experienced severe stress.

IL-18 Gene Promoter Polymorphisms are Involved in Periodontal Disease: A Meta-Analysis

Microbial plaque that builds up in the gingival crevice area causes inflammation and leads to periodontal disease. Previous research has shown an association between interleukins with periodontitis. The association between interleukin-18 (IL-18) gene polymorphism and periodontitis risk was studied extensively, but the results are contradictory. The aim of this study is to find the association of two IL-18 promoter variants namely -607 C > A (rs1946518) and -137 G > C (rs187238), and the risk of chronic and aggressive periodontal disease by meta-analysis. The databases of PubMed, Medline, Web of Science, and Google Scholar were all explored to find the appropriate studies. The MetaGenyo software was used to calculate each analysis. Outcomes of the pooled analyses revealed significantly elevated risk for periodontitis for both polymorphisms. There is no significant heterogeneity between studies. No significant publication bias was observed. This meta-analysis provided the evidence of a link between IL-18 gene polymorphism in periodontitis.

Ассоциация промоторного полиморфизма гена TNF-α с первичной открытоугольной глаукомой

Background: glaucoma is one of the leading causes of blindness worldwide. Diagnosis of glaucoma at an early stage is challenging. Therefore, genetic factors predisposing to the development of primary open-angle glaucoma (POAG) are investigated. One of these predictors is tumor necrosis factor α (TNFα), a multifunctional proinflammatory cytokine involved in glaucoma pathogenesis. Point mutations in the regulatory region of the TNFα gene are hypothesized to be associated with POAG risk. Aim: to analyze the polymorphism of three positions of TNFα gene promoters and their complexes in West Siberian Caucasians with POAG and healthy volunteers. Patients and Methods: the study enrolled 401 individuals, i.e., 99 patients with POAG stage 2 and 302 individuals without POAG (randomized control group). All participants signed an informed consent form. Single nucleotide TNFα gene promoter polymorphism (rs361525, rs1800629, rs1800630) was analyzed. Genotyping was performed by restriction analysis of gene amplification products. Results: the occurrence of minor genotype TNF-308*АА was significantly higher in POAG (odds ratio 11.41, p=0.0011). The occurrence of two other genotypes demonstrated no significant differences between groups. Three complex genotypes were positively associated with POAG (TNF-863*CC:TNF-308*AA, TNF-308*AA:TNF-238*GG и TNF-863*CC:TNF-308*AA:TNF-238*GG). We failed to identify any single nucleotide polymorphism or complexes negatively associated with POAG. Conclusion: minor genotype TNF-308*АА is an essential factor of POAG pathogenesis. Two other polymorphic gene variants were associated with POAG as a part of complex genotypes. These findings demonstrate that potential polymorphic associations should be considered in the case-control analysis. Keywords: primary open-angle glaucoma, polymorphism, TNFα gene, gene promoter, complex genotypes. For citation: Shevchenko A.V., Prokof’ev V.F., Konenkov V.I. et al. Association of TNF-α gene promoter polymorphism with primary open-angle glaucoma. Russian Journal of Clinical Ophthalmology. 2022;22(1):11–15 (in Russ.). DOI: 10.32364/2311-7729-2022-22-1-11-15.

P.0318 Unhealthy lifestyle is associated with risk-taking in traffic and moderated by the serotonin transporter gene promoter polymorphism

P.0318 Unhealthy lifestyle is associated with risk-taking in traffic and moderated by the serotonin transporter gene promoter polymorphism

Association between HO‑1 gene promoter polymorphisms and diseases (Review).

Heme oxygenase-1 (HO-1) is an inducible cytoprotective enzyme that degrades heme into free iron, carbon monoxide and biliverdin, which is then rapidly converted into bilirubin. These degradation products serve an important role in the regulation of inflammation, oxidative stress and apoptosis. While the expression level of HO-1 is typically low in most cells, it may be highly expressed when induced by a variety of stimulating factors, a process that contributes to the regulation of cell homeostasis. In the 5′-non-coding region of the HO-1 gene, there are two polymorphic sites, namely the (GT)n dinucleotide and T(−413)A single nucleotide polymorphism sites, which regulate the transcriptional activity of HO-1. These polymorphisms have been shown to be closely associated with the occurrence and progression of numerous diseases, including cardiovascular, pulmonary, liver and kidney, various types of cancer and viral diseases. The present article reviews the progress that has been made in research on the association between the two types of polymorphisms and these diseases, which is expected to provide novel strategies for the diagnosis, treatment and prognosis of various diseases.

Association of Tumor Necrosis Factor-α Gene Promoter Polymorphisms with Periodontitisin Type II Diabetic Syrian Population

Association of Tumor Necrosis Factor-α Gene Promoter Polymorphisms with Periodontitisin Type II Diabetic Syrian Population

The IL-22 gene rs2227478 polymorphism significantly decreases the risk of colorectal cancer in a Han Chinese population

To examine the role of IL-22 gene in colorectal cancer (CRC) susceptibility, we identified causative genetic polymorphisms in promoter region of IL-22 gene and explored the mechanism underlying their contribution to CRC development in a Chinese population of Hubei province. 13 target single nucleotide polymorphisms (SNPs) in IL-22 gene promoter were genotyped in 787 CRC patients (426 colon cancer and 361 rectal cancer) and 800 normal controls. The results demonstrated that the rs2227478 T > C polymorphism was significantly associated with the risk of colon cancer, rectal cancer and CRC, and the C allele was associated with a decreased cancer risk than the T allele. In CRC tissue samples, the subjects with CT+CC genotypes of rs2227478 had lower levels of IL-22 mRNA than the subjects with TT genotypes. Further functional analysis revealed that the transcription repressor Sp1 possessed a higher binding affinity to the C allele than the T allele. Collectively, the rs2227478 T > C is a functional genetic polymorphism that significantly reduces the CRC risk in a Han Chinese population.

Association between eNOS gene promoter polymorphism (-786T&gt;C) and idiopathic recurrent pregnancy loss in Iranian women

Objective: To investigate the frequency of -786T&gt;C variant in endothelial nitric oxide synthase (eNOS) gene promoter in Iranian women with recurrent pregnancy loss. Methods: Blood samples were obtained from 100 unrelated women affected by recurrent pregnancy loss and 100 unaffected women as the controls. Genomic DNA was extracted and -786T&gt;C polymorphism in eNOS gene promoter was investigated by PCR-RFLP method. Statistical analyses and Hardy-Weinberg equilibrium in the groups of patients and controls were performed by Chi-square test and SPSS standard software (Version 21). Results: The frequency of homozygous TT was 40% in cases and 46% in the control group; the frequency of CC was 7% in cases and 5% in the control group; frequency heterozygote TC was 53% in cases and 49% in the control group. Genotype frequencies between the two groups showed no significant differences (P&gt;0.05). Conclusions: The -786T&gt;C polymorphism is not more frequent in recurrent pregnancy loss in this population.

Significance of genetic modifiers of hemoglobinopathies leading towards precision medicine

Hemoglobinopathies though a monogenic disorder, show phenotypic variability. Hence, understanding the genetics underlying the heritable sub-phenotypes of hemoglobinopathies, specific to each population, would be prognostically useful and could inform personalized therapeutics. This study aimed to evaluate the role of genetic modifiers leading to higher HbF production with cumulative impact of the modifiers on disease severity. 200 patients (100 β-thalassemia homozygotes, 100 Sickle Cell Anemia), and 50 healthy controls were recruited. Primary screening followed with molecular analysis for confirming the β-hemoglobinopathy was performed. Co-existing α-thalassemia and the polymorphisms located in 3 genetic loci linked to HbF regulation were screened. The most remarkable result was the association of SNPs with clinically relevant phenotypic groups. The γ-globin gene promoter polymorphisms [− 158 C → T, + 25 G → A],BCL11A rs1427407 G → T, − 3 bp HBS1L-MYB rs66650371 and rs9399137 T → C polymorphisms were correlated with higher HbF, in group that has lower disease severity score (P < 0.00001), milder clinical presentation, and a significant delay in the age of the first transfusion. Our study emphasizes the complex genetic interactions underlying the disease phenotype that may be a prognostic marker for predicting the clinical severity and assist in disease management.

Association of a novel Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)-3928C/T and GM-CSF(3606T⁄C) Promoter gene polymorphisms with the pathogenesis and severity of acne vulgaris: A case-controlled study.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is believed to play an important role in the development of acne vulgaris. To investigate the presence of GM-CSF 3928C/T and GM-CSF 3606T/C promoter gene polymorphisms in Egyptian acne patients. To examine whether GM-CSF single nucleotide polymorphisms (SNPs) are associated with susceptibility to acne vulgaris (AV), we investigated the genotype and allele frequencies of the SNP 3928C/T and 3606T⁄C of the GM-CSF gene in 100 Egyptian acne patients (29 with mild acne, 38 with moderate acne, and 33 with severe acne) and 100 controls, using a PCR restriction fragment length polymorphism (RFLP) method. There was a highly significant difference in genotype and allele frequencies of the 3928C/T group between patients with acne vulgaris and controls for the SNP site. Regarding the 3606T/C subgroup only a marginal significant difference was found between cases and controls in TC pattern (p=0.039); with the TC genotype appearing more in cases (53% of patients) than controls (35% of healthy controls). We report a novel GM-CSF 3928C/T promoter gene polymorphism contributing to the pathogenesis of acne in Egyptian population.