Differences In Allele Distribution Research Articles

English

BACKGROUND Coronary artery disease is multifactorial in origin. Coronary artery disease predisposition is attributed to genetic factors also. Many gene polymorphisms are implicated out of which paraoxonase 1 (PON 1) gene is an important one. The product of paraoxonase gene is paraoxonase enzyme which is seen in serum associated with high density lipoprotein (HDL). This enzyme is mainly synthesised by the liver. The protective effect of HDL is attributed to the presence of such enzymes on it. Gln to Arg polymorphism at position 192 confers a risk of developing atherosclerosis and coronary artery disease (CAD). This study is done to assess the genotype distribution of PON 1 gene in CAD patients compared to healthy controls in a population from Kerala. METHODS The case group consists of 100 angiographically proven CAD patients with no history of hypertension, diabetes mellitus, hepatic disease or smoking. The control group had 100 healthy controls from the general population. PON 1 gene was amplified by a polymerase chain reaction (PCR) technique already reported and restriction fragment length polymorphism by the restriction enzyme Alwl was done to assess the polymorphism. to assess the polymorphism. RESULTS In this study, the frequency of heterozygous genotype QR was 86 % in control and 76 % in cases. Though there was no significant difference in allele distribution of Q or R, RR genotype was significantly higher in the case group ( 2 = 8.82; p value = .012). With binary logistic regression model, adjusting for age and sex, RR genotype is independently associated with CHD. Adjusted odds ratio of RR was 5.24 with 95 % confidence interval (CI) 1.41 - 19.47 for developing CHD (p < 0.05). CONCLUSIONS The RR genotype is more frequently seen in CAD patients than in controls. The QR genotype is more frequent than QQ or RR in both cases and controls. KEYWORDS Coronary Artery Disease, Paraoxonase, Gene Polymorphism

Role of PVT1 polymorphisms in the glioma susceptibility and prognosis.

Genetic factors play a crucial role in the glioma risk and prognosis of glioma patients. To explore the role of plasmacytoma variant translocation 1 (PVT1) polymorphism in the susceptibility and survival of glioma in the Chinese Han population, we conducted a case-control study. The three single-nucleotide polymorphisms (SNPs) in PVT1 were genotyped using Agena MassARRAY from 575 patients with glioma and 500 healthy controls. We used the χ2 test to analyze the differences in distribution of allele and genotype between the cases and controls. Odds ratio and 95% confidence interval (CI) were calculated by logistic regression analysis to evaluate the association SNPs with glioma risk. The effects of polymorphisms and clinical features on survival of glioma patients were evaluated using the log-rank test, Kaplan-Meier and Cox regression analysis. We found that rs13255292 was associated with a decreased risk of glioma in the recessive model in overall or male; and rs4410871 was significantly associated with an increased the risk of glioma in age ≤40 years old or female. Moreover, the extent of resection and chemotherapy were found to be key prognostic factors in survival of glioma patients. However, the gender, age, tumor grade, radiotherapy and PVT1 polymorphisms have no effect on prognosis of glioma patients. Our results indicated that PVT1 polymorphisms (rs13255292 and rs4410871) were associated with glioma susceptibility, but have no effect on prognosis of glioma patients. Further studies with large samples are required to confirm the results.

Алельний поліморфізм мікросателітних локусів ДНК яєчних курей

The analysis of allelic polymorphism of five industrial egg crosses of chickens by five microsatellite DNA loci (ADL0268, MCW216, LEI0094, ADL0278, and MCW248) was carried out. DNA loci were chosen according to the recommendations of the International Society for Animal Genetics (ISAG). Based on the results of mathematical-statistical processing and data analysis, the spectra and frequencies of allelic variability, the peculiarities of allele pools, were identified, and unique alleles were identified. In general, the species Gallus gallus is characterized by a specific character of allelic spectra for all investigated microsatellite DNA loci (P <0.001). The highest rates of allelic variability were recorded in brown crosses "Lohmann brown" and "Hisex brown" (Na (LimNa)=(9.2 (5-17) and 7.4 (6-11), respectively). The studied crosses were characterized by a shift in allelic spectra towards a decrease in the fragment length. “Lohmann white” stands out among the birds of other crosses by high consolidation for individual alleles for all studied microsatellites (from ADL278114 – 0.343 and ADL268108 – 0.485 to LEI094259 – 0.720, MCW0248213 – 0.785 and MCW0216137 – 0.920). Unique alleles with the highest frequency were found in brown cross chickens, and in the “Hy-Line W-98” bird, they were not found. The number of unique alleles identified varied from 1 ("Hisex white") to 11 ("Lohmann brown"). Locus LEI094 turned out to be the most polymorphic in terms of the number of unique alleles – 10 such allelic variants were identified for it. No unique alleles were identified at the ADL0268 locus. The obtained estimates criterion χ2 of K. Pearson indicate significant differences in the frequency distribution of alleles for all studied loci. When using the MICROSATELLITE ANALYSER software, it was found that the nature of the variability of the studied microsatellite DNA loci in five industrial crosses of the egg chickens, both in the number of identified alleles and in the nature of their distribution, corresponded to the stepwise mutation model (SMM).

Correlations of UGT1A1 gene polymorphisms with onset and prognosis of non-small cell lung cancer.

The aim of this study was to investigate the correlations of UDP glucuronosyltransferase family 1 member A1 (UGT1A1) gene polymorphisms with the onset and prognosis of non-small cell lung cancer. A total of 400 patients with non-small cell lung cancer (disease group) and healthy controls (control group) in our hospital were selected as research subjects. Genomic DNA was extracted from the peripheral blood. UGT1A1 gene polymorphisms rs8330, rs4148323 and rs35003977 were detected after Polymerase Chain Reaction (PCR) amplification. RT-qPCR was performed to measure the expression level of UGT1A1. The survival of patients was analyzed combined with their prognosis. Moreover, the expression of UGT1A1 gene in lung cancer patients from The Cancer Genome Atlas (TCGA) database was analyzed by bioinformatics, and the prognosis was analyzed. According to the expression level of UGT1A1 gene from TCGA and GTEx databases, UGT1A1 gene was highly expressed in lung cancer tissues but lowly expressed in normal lung tissues, and the difference was statistically significant (p<0.05). Combined with the expression level of UGT1A1 and the prognostic information of lung cancer patients from TCGA database, patients with higher expression level of UGT1A1 gene exhibited significantly better prognosis than those with lower level (p=0.0013), suggesting that UGT1A1 gene is an anti-oncogene. There were statistically differences in allele distribution of UGT1A1 gene polymorphism rs8330 between the disease group and control group (p=0.003), and the frequency of allele G was higher in disease group. Moreover, the distribution of genotypes of UGT1A1 gene polymorphisms rs8330 (p=0.006) and rs4148323 (p=0.003) in the disease group was significantly different from that in the control group, and the frequencies of GG genotype of polymorphisms rs8330 and rs4148323 were higher in the disease group. Statistically significant differences in the distribution of recessive models of UGT1A1 gene polymorphism rs8330 were observed between the disease group and control group (p=0.047), and the disease group exhibited a lower frequency of recessive model GC + CC than control group. There were evident differences in the distribution of haplotype GGT of UGT1A1 gene polymorphisms rs8330, rs4148323 and rs35003977 between the disease group and control group (p=0.004), and the frequencies of haplotype GGT were higher in the disease group than those in the control group. UGT1A1 gene polymorphism rs8330 was remarkably associated with gene expression (p<0.05). Meanwhile, the expression of UGT1A1 gene in patients carrying genotype CC declined notably compared with that in patients carrying genotypes GG and GC (p<0.05). Furthermore, the polymorphism rs8330 had a significant correlation with the survival of patients in disease group (p=0.0001), and patients with genotype CC had the worst prognosis. UGT1A1 gene polymorphisms are prominently correlated with the onset and prognosis of non-small cell lung cancer.

STAT3 gene polymorphism in chronic obstructive pulmonary disease.

The aim of this study was to explore the correlation between rs8069115, rs41289087, and rs11079042 polymorphisms of the signal transducer and activator of transcription 3 (STAT3) gene and chronic obstructive pulmonary disease (COPD). A total of 200 patients diagnosed with COPD were enrolled in the disease group. Meanwhile, 200 normal subjects were selected as the control group. Peripheral blood was collected from subjects in the disease group and control group. Subsequently, nucleated cells were isolated for determination of STAT3 gene polymorphisms. Quantitative Polymerase Chain Reaction (qPCR) was utilized to detect the expression level of STAT3. Samples from 12 patients with differences in STAT3 haplotypes and 12 cases with no difference were collected and treated with transcriptome sequencing to analyze pathways enriched with differentially expressed genes. There were statistically significant differences in allele distributions at rs8069115 between the disease group and control group (p=0.000), and the allele frequency of G was higher in disease group. Genotype distributions of rs8069115 (p=0.000) and rs41289087 (p=0.000) of the STAT3 gene in disease group were significantly different in comparison with the control group. The frequency of rs8069115 GG genotype was remarkably higher, while the frequency of rs41289087 TG genotype was lower in the disease group (p<0.05). In addition, compared with the control group, the distributions of the dominant model (p=0.002) and recessive model (p=0.004) of rs8069115 of the STAT3 gene were markedly different in the disease group. A significantly higher frequency of dominant model GG+GA and lower frequency of recessive model GA+AA were observed at rs8069115 in the disease group (p<0.05). Moreover, the haplotype distributions of AGC (p=0.002), ATC (p=0.001), GTA (p=0.010), and GTC (p=0.035) at rs8069115, rs41289087, and rs11079042 were different between the disease group and control group. Besides, rs8069115 locus and rs11079042 locus were linked to each other (D'=0.523). There was a remarkable association between rs11079042 polymorphism of the STAT3 gene and gene expression (p<0.05). STAT3 was highly expressed in patients with genotype CC (p<0.05). Furthermore, changes in transcriptome levels among different haplotype populations (haplotype with different distributions vs. haplotype with no difference in distribution) were analyzed. The results demonstrated that multiple pathways, such as ECM-receptor interactions, cell cycle checkpoints, and protein processing were notably enriched (p<0.05). According to our results, we confirmed that the polymorphisms (rs8069115, rs41289087, and rs11079042) of STAT3 gene are noticeably correlated with the occurrence and progression of COPD.

FEATURES OF THE IMMUNOGENETIC STRUCTURE OF PIGS OF DOMESTIC BREEDS, SUITABLE FOR XENOTRANSPLANTATION

The aim of the work was to determine the immunogenetic characteristics of pigs of two Ukrainian breeds by their adaptability, resistance, reproduction, genetic homogeneity, the presence of alleles that determine the potential suitability for use in xenotransplantation and other biomedical purposes. At present, there is no breed or specialized line of pigs in Ukraine to address the urgent problems of humane medicine. However, there is a favorable situation for the creation of such a breed or the withdrawal of a specialized line because of the demand of pharmacological concerns for model biological objects to study the mechanisms of action of modern medical preparations, to develop methods of conducting bloodless surgical operations, modeling of the clinic and epidemiology of infectious diseases of different diseases. immune response, etc. In this context, there was a compelling reason to preserve the indigenous breeds of pigs of Ukraine, especially Ukrainian meat and Мyrgorod. Standard methods of immunogenetic analysis of pigs were used. The erythrocyte antigens of 9 blood group systems were determined using specific immune sera and the involvement of a bank of immunodiagnostics meeting international requirements. Blood groups were determined by the reaction of agglutination, an indirect Coombs test, and a hemolytic test. Statistical processing of the research results was performed using mathematical statistics using the GenAlex-6.0 computer program. As a result of the immunogenetic analysis of Ukrainian beef and myrrh-pig breeds, it was determined that each of them is characterized by a specific immunogenic profile, which is related to both breed characteristics and differences, and methods of their breeding. The difference between the distribution of the overwhelming number of alleles of blood groups was statistically significant. Pigs of Ukrainian meat and Мyrgorod breeds had the largest differences in allele distribution by B, E, F, K, L blood group systems with the presence of the Ladhjk marker allele in the latter (p &lt; 0.05). The specificity of immunogenic profiles was evaluated, depending on the history of creation and the direction of the animal's performance. Species of Myrhorod and Ukrainian meat breeds with the presence of genotypes A - / - and Ebdgkmp / bdgkmp were found to determine the suitability of animals for xenotransplantation. Of the 80 animals tested for immunogenetic markers, only 24 individuals met the established selection criteria. The range of determined indicators of actual homozygosity for selected genotype animals ranged from 55.56% to the maximum value – 88.89%, mainly in sows from the Smorodinа, Rusalkа, Sorokа and Soyka families. According to molecular genetic analysis, you have been informed that the established criteria of the biomedical model meet only 13 individuals of Ukrainian meat breed. Among animals with the highest index of actual homozygosity, representatives of Cererа and Cіlina were identified, with Celina 4092 being homozygous for all blood group systems studied. The selection of pigs for blood alleles, desirable for xenotransplantation, with their transfer to the homozygous state: A -/- and Ebdgkmp / bdgkmp will impair the adaptive, first of all, reproductive qualities of the animals and create significant problems for the cultivation of such individuals. The possibility of the occurrence of reproductive and resistance disorders of pigs in the selection of blood groups genotypes modeled for xenotransplantation and the search for ways to overcome them are being considered.

ASSOCIATION OF ENAM C2452T POLYMORPHISM WITH HIGH RATES OF CARIES OCCURRENCE IN AN INDONESIAN POPULATION

Objective: Tooth decay or the caries process is a common dental problem that affects millions of people worldwide. Many risk factors are modifiable,while others are not (e.g., genetic factors). Polymorphism of the enamelin (ENAM) gene, which is required to ensure production of an essentialprotein for enamel development, may pose as a risk factor for the caries process. This study sought to investigate the possibility of ENAM C2452Tpolymorphism acting as a risk factor in the caries process.Methods: The polymerase chain reaction–restriction fragment length polymorphism method was employed to evaluate DNA samples taken from 95subjects with a high caries prevalence and 89 control subjects for ENAM C2452T polymorphism.Results: Based on Chi-squared tests, there were significant genotype and allele distribution differences between the group with a high cariesprevalence and the control group (p=0.005 and p=0.007). Polymorphism in this context may, therefore, serve as a risk factor for caries onset andprogression (OR: 3.62).Conclusion: ENAM C2452T polymorphism is related to the caries process and may constitute a risk factor.

Relationship between URAT1 Gene Polymorphism and Uric Acid-Lowering Effect of Losartan in Hypertensive Patients with Hyperuricemia

To investigate the relationship between urate iransporter-1 gene polymorphism and the uric acid-lowering effect of losartan in hypertensive patients complicated with hyperuricemia, polymerase chain reaction-restriction fragment length polymorphism was used to identify the genotypes of 100 hypertensive patients with hyperuricemia and 100 healthy controls. The experimental group patients received oral administration of 100 mg losartan for 14 d. Blood pressure, uric acid, creatinine, blood urea nitrogen, triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, small and dense low-density lipoprotein cholesterol and fasting plasma glucose were measured before and after treatment. There was no significant difference in the frequency distribution of alleles and genotypes of rs7929627, rs75786299 and rs3825017 between the two groups. After treatment, the levels of uric acid, creatinine, blood urea nitrogen and fasting plasma glucose were significantly decreased and the levels of uric acid and creatinine in hypertensive patients with hyperuricemia were significantly lower than those with TT genotype (p<0.05). The rs7929627, rs75786299, and rs3825017 of the URAT1 gene could affect the uric acid-lowering effect of losartan.

HLA-DRB1 differences in allelic distribution between familial and sporadic multiple sclerosis in a Hellenic cohort

ABSTRACTObjective: Familial Multiple Sclerosis (fMS) is reported to have distinct clinical and imaging characteristics in comparison to the sporadic disease (sMS). Nevertheless, the genetic/immunogenetic profile of fMS has never been investigated in depth, so far. In this study, we examined differences of HLA-DRB1 allelic frequencies between 57 fMS and 141 sMS Hellenic patients, with reference to 246 previously genotyped healthy controls (HCs).Patients and Methods: All patients underwent medical interview and DRB1 genotyping, using a low-resolution SSOP technique. Statistical analyses were performed using SPSS v.21.0 software, with significance set at 0.05, and p value corrected according to the Benjamini–Yekutieli method.Results: 29 fMS cases had at least one 1st degree relative affected (fMS 1st), while the rest had at least one 2nd or 3rd degree relative affected (fMS 2nd/3rd). Parent-of-origin effects were observed, with the prevalence of maternal inheritance. Frequency of DRB1*15 was significantly increased in fMS and sMS, in comparison to HCs (p = 0.002 and <0.001, respectively). After fMS stratification, this result was mainly attributed to the fMS 2nd/3rd subgroup. DRB1*11 frequency was significantly decreased only in sMS (p < 0.001) with fMS approximating HCs’ frequency, especially for the fMS 1st subgroup. Heterozygosity was favored over homozygosity in all groups.Conclusion: We propose possible HLA-DRB1 allelic distribution differences between fMS and sMS, which become more apparent as proximity of affected relative/-es in fMS increases, supporting a rather degraded role of DRB1 alleles in fMS HLA/immunogenetics and indicating the concomitant implication of other HLA and non-HLA polymorphisms.

Association of vascular endothelial growth factor (VEGF) Gene polymorphisms and expression with the risk of endometriosis: a case-control study.

Endometriosis is a polygenic and multifactorial gynecology situation which might be associated with angiogenesis. In the current study we assess the role of vascular endothelial growth factor (VEGF) - 2578 A/C, and + 936 C/T polymorphisms in susceptibility to endometriosis and checking the expression of VEGF mRNA in eutopic tissue of endometrium with and without endometriosis. The study was comprised of 300 patients who underwent laparascopic or laparotomy surgery with 100 cases who had confirmed histological diagnosis of endometriosis, and 200 controls with no histological diagnosis of disease. The genotyping of VEGF polymorphisms was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique and the gene expression in tissue was determined using Real-Time PCR assay. There was no important difference of allele distribution of the - 2578 A/C (P = 0.7) and + 936 C/T (P = 0.5) polymorphisms among endometriosis cases and controls. Study of VEGF expression during the menstrual cycle, showed that endometrial tissue in cases group expressed more VEGF mRNA at the secretory phase compared to the proliferative phase (P = 0.03). Our results suggest that - 2578 A/C and + 936 C/T polymorphisms of VEGF did not seem to have impact on endometriosis predisposition in our study population. Also we did not find any link between VEGF mRNA expression and risk of endometriosis.

Evaluation of IL6, IL10 and VDR alleles distribution in an Italian large sample of subjects affected by chronic periodontal disease.

In recent decades, the role played by the immune response to bacteria in the pathogenesis of chronic periodontal disease (PD) has long been studied. Although from the clinical point of view, adequate oral hygiene is essential to ensure a satisfactory response of the host to infections, modulation of the reaction of immune system could be influenced by genetic factors. The aim of the present study was to investigate the distribution of alleles of polymorphisms relevant for chronic periodontitis in a sample of adult subjects affected by chronic PD. The present study was conducted with sample collected in Italian private practice offices from January 2013 to December 2017. The sample included 744 adult patients diagnosed with chronic periodontitis. The inclusion criteria were as follows: age > 18 years, diagnosis of chronic PD. The diagnosis of chronic periodontitis was based on the criteria established by the American Academy of Periodontology. No significant difference in allele distribution among patients from different Italian regions was found. Results, supporting absence of population heterogeneity for the investigated polymorphisms in Italy, suggest similar effect in periodontitis etiology.

2502. Host Susceptibility to Andes Hantavirus Infection Associates to a Single Nucleotide Polymorphism at the αVβ3 Integrin

BackgroundANDV is etiologic agent of hantavirus cardiopulmonary syndrome (HCPS) in Chile. Transmission occurs mainly by exposure to aerosolized excretes of infected rodents, person-to-person transmission has also been reported. ANDV infected endothelial cell through αV,β3 integrin at plexin-semaphorin-integrin (PSI) domain. In vitro assays establish that the change from leucine to proline, at residues 33 in PSI-domain inhibits ANDV recognition of integrin. Here we assessed the risk that represents a polymorphism leucine to proline (L33P) and the association to susceptibility to ANDV.MethodsFor risk assessment, 74 cases and 105 controls (exposed but not infected) were genotyped by Taqman assay, epidemiological and demographic data were recorded. We also evaluated SNP distribution at general population, infected population (serum collection) and 11 prospectively diagnosed ANDV cases. A regression logistic model was used to assess environmental or person to person risks factors of hantavirus infection either in presence or absence of the “susceptible” or “protective” genotypes.ResultsIn cases and controls the susceptible (TT) genotype (Leucine) was distributed in an 89.2 and 60%, respectively (Figure 1). The protective genotype (CC) was absent among cases but present at 11.4% in exposed controls. We estimated the Odds ratio (OR), through a logistic model, first using only previously described risk activities and after adding the genotype TT; the OR increased from 6.2 to 12.6. Cases and control at same exposure (access to abandoned place) showed that controls have a 57% of TT genotype, meanwhile in cases was 91%, with an OR of 7.3. For a second common exposure activities (handle woods) the controls had a 59.4% of TT genotype, meanwhile for cases 85%. For general and infected population both did not show statistical differences in allele distribution, and we detected a 1.7% of CC genotype in the infected population (Figure 2). We did not detected CC genotypes in the eleven prospective ANDV cases.ConclusionThere was association between this particular SNP and infection susceptibility to ANDV. We highlight the relevance of genetic background in host-virus interaction. Nevertheless, other factors such as innate immune system or viral variability must be explored to fully understand the disease pathogenesis.Disclosures C. Martinez-Valdebenito, FONDECYT1161197: Grant Investigator, Educational grant. ACT1408: Grant Investigator, Research grant. M. Ferres, FONDECYT1161197: Grant Investigator, Research grant. ACT1408: Grant Investigator, Research grant. N. Le Corre, FONDECYT1161197: Grant Investigator, Research grant. ACT1408: Grant Investigator, Research grant. J. Angulo, FONDECYT1161197: Grant Investigator, Research grant. ACT1408: Grant Investigator, Research grant.

Association of M470V polymorphism of CFTR gene with variability of clinical expression of asthma: Case-report study

Introduction and ObjectivesAsthma is a complex genetic disorder. Several genes have been found associated with asthma. The cystic fibrosis transmembrane conductance regulator (CFTR) gene is one of them. The aim of this study was to perform a comparative analysis of the genotype and allele frequency distributions of the biallelic marker M470V within the CFTR gene on mutant and wide chromosomes. Patients and methodsThe molecular approach consists in the genotyping of the M470V marker by the PCR-RFLP technique in 105 asthmatic patients, aged between four months and 17 years, and 105 healthy subjects. ResultsWe found a significant difference in the genotype frequencies between the two studied groups (χ2=9.855, P=0.007). The V/V genotype was over represented in the asthmatic group as compared to the controls (32.38% vs. 16.19%). Whereas, the M/V genotype is more frequent in healthy subjects (40.95% vs. 28.71%). We also noted a significant difference in allelic distribution of M470V with associated diseases (χ2=9.610, P=0.022). ConclusionsThe present study is the first report on the distribution of the M470V polymorphism in asthmatic Tunisian patients. We noticed that the M470V variant could modulate the clinical phenotype of asthmatic patients. This preliminary study will establish the molecular basis of this disease in Tunisia.

The FOXP3 rs3761547 Gene Polymorphism in Multiple Sclerosis as a Male-Specific Risk Factor

The FOXP3 gene encodes a transcription factor and is predominantly expressed in the CD4+CD25+ regulatory T cells which plays a pivotal role in the maintenance of immune homeostasis. The defect of FOXP3 gene may provide a critical link between autoimmunity and immune deficiency. The purpose of our study was to evaluate the association of chosen polymorphisms of FOXP3 gene (rs3761549, rs3761548, rs3761547) with different clinical multiple sclerosis (MS) data of our relapsing-remitting groups of patients and in control group. The study was performed on a group consisting of 174 relapsing-remitting MS patients, diagnosed under 40 years of life, and 174 healthy volunteers. Genotyping was performed using a real-time PCR-based method by TaqMan Assays. Significant differences in distribution of allele C rs3761547 were found in male MS patients in comparison to the male healthy group (p = 0.046, OR 1.95, CI 95%). No association between MS and the other two polymorphisms was observed in males and females of both studied groups. Our data may suggest that FOXP3 rs3761547 gene polymorphism are related notably with the increased risk of MS development in males patients. To our knowledge this is the first study which indicates gender-specific relation between rs3761547 FOXP3 gene polymorphism and multiple sclerosis.

FADS1-FADS2 and ELOVL2 gene polymorphisms in susceptibility to autism spectrum disorders in Chinese children

BackgroudAutism spectrum disorders (ASD) are a complex group of neurodevelopmental disorders with a genetic basis. The role of long-chain polyunsaturated fatty acids (LC-PUFAs) and the occurrence of autism has been the focus of many recent studies. The present study investigates whether genetic variants of the fatty acid desaturase (FADS) 1/2 and elongation of very long-chain fatty acids protein (ELOVL) 2 genes, which are involved in LC-PUFA metabolism, are associated with ASD risk.MethodsA cohort of 243 ASD patients and 243 unrelated healthy controls were enrolled in this case control study. Sixteen tag single nucleotide polymorphisms from the FADS1–2 and ELOVL2 genes were genotyped using the Sequenom Mass Array.ResultsThere were significant differences in allelic distribution of FADS2 rs526126 (OR = 0.55, 95% CI = 0.42–0.72, pFDR < 0.05) between autistic children and controls. FADS2 rs526126 and ELOVL2 rs10498676 were associated with decreased ASD risk in recessive model (OR = 0.07, 95% CI = 0.02–0.22, pFDR < 0.01; OR = 0.56, 95% CI = 0.35–0.89, pFDR = 0.042), while ELOVL2 rs17606561, rs3756963, and rs9468304 were associated with increased ASD risk in overdominant model (OR = 1.63, 95% CI = 1.12–2.36, pFDR = 0.036; OR = 1.64, 95% CI = 1.14–2.37, pFDR = 0.039; OR = 1.75, 95% CI = 1.22–2.50, pFDR = 0.017). The A/A genotype of rs10498676 was correlated with a decline in the Autism Diagnostic Interview-Revised communication (verbal and nonverbal) domain.ConclusionsThese findings provide evidence of an association between FADS2 and ELOVL2 polymorphisms and ASD susceptibility in Chinese children.

Associations of serotonin transporter gene promoter polymorphisms and monoamine oxidase A gene polymorphisms with oppositional defiant disorder in a Chinese Han population

BackgroundOppositional defiant disorder (ODD) is a behavioral disorder that mainly refers to a recurrent pattern of disobedient, defiant, negativistic and hostile behaviors toward authority figures. Previous studies have showed associations of serotonin transporter (5-HTT) and monoamine oxidase A (MAOA) with behavioral and psychiatric disorders. The purposes of this study were to investigate the potential association of 5-HTT gene promoter polymorphism (5-HTTLPR) and MAOA gene polymorphism with susceptibility to ODD in a Han Chinese school population.MethodsThe 5-HTTLPR gene polymorphism and the MAOA gene polymorphism were genotyped in a case–control study of 257 Han Chinese children (123 ODD and 134 healthy controls).ResultsThere was significant difference in the allele distribution of 5-HTTLPR (χ2 = 7.849, P = 0.005) between the ODD and control groups. Further, there were significant differences in genotype (χ2 = 5.168, P = 0.023) and allele distributions (χ2 = 10.336, P = 0.001) of the MAOA gene polymorphism that is variable-number tandem repeat (MAOA-uVNTR) between two groups. Moreover, there were significant differences in genotype (χ2 = 4.624, P = 0.032) and allele distributions (χ2 = 9.248, P = 0.002) of MAOA-uVNTR only in the male ODD and healthy groups.ConclusionsOur results suggest that 5-HTTLPR and MAOA-uVNTR gene variants may contribute to susceptibility to ODD. Further, MAOA-uVNTR gene polymorphism may play a role in susceptibility to ODD only in male children.

Association of Single-Nucleotide Polymorphisms of CD44 Gene with Susceptibility to Breast Cancer in Chinese Women.

BackgroundThis study aimed to evaluate the association of CD44 gene single-nucleotide polymorphisms with susceptibility to breast cancer.Material/MethodsThis case-control study included 242 breast cancer patients and 252 normal people without disease. The single-nucleotide polymorphisms of the CD44 gene in the 2 groups were genotyped by PCR-LDR method. The OR and its 95% CI was calculated by chi-square test and logistic regression analysis. The construction of haplotypes and their interaction analysis with relevant factors were carried out by SHEsis and SNPStats online.ResultsThe genotype distribution of CC and CT, CC and CC+CT, and CC+CT and TT in rs13347 showed a significant difference between cases and controls, and the difference in distribution of alleles C and T was statistically significant. The genotype and alleles distribution of rs4756195 and rs8193 showed no statistically significant difference (P>0.05). The haplotypes distribution of CAC, CGT, TAC, and TGT showed a significant difference between the 2 groups (P<0.05). The results of analysis of haplotypes and their interactions with relevant factors showed that breast cancer risk in the PR-negative group was significantly higher than that in the PR-positive group (P=0.016). We found an interaction between haplotypes and PR status.ConclusionsThe genotypes CT, CT+TT, TT, and allele T in rs13347 may be risk factors for breast cancer. The haplotype CAC may be a protective factor against breast cancer, and CGT, TAC, and TGT may be risk factors for breast cancer. The PR status interacts with CD44 gene SNP.

Differences in SNP genotype distributions between complex and simple suicides.

Dysregulations in serotonin neurotransmission can be a strong contributing factor in suicide and impulsive-aggressive personality traits. Victims of suicide form a heterogeneous group in terms of planning, lethality and number of used methods. In this study, we tested single nucleotide polymorphisms (SNPs) of the monoamine oxidase (MAO) A and B genes on the Slovenian population, which has one of the highest suicide rates in the world. Genotyping was performed on 77 victims of complex suicide, 406 victims of simple suicide and 289 controls. The differences in allele distribution were investigated with the two-tailed χ2 test. Haplotype analysis was performed on 740 subjects. Significant or tendency for significant differences in distribution was observed for all studied polymorphisms in the MAOA gene when comparing male victims of complex suicide, victims of simple suicide and controls. Minor allele frequencies in male victims of complex suicide were A 6.7% for rs3027407, C 13% for rs909525 and T 12.7% for rs1137070; in victims of simple suicide, A 36.3% for rs3027407, C 39.5% for rs909525 and T 36.4% for rs1137070; and in controls, A 25.2% for rs3027407, C 30.4% for rs909525 and T 25.8% for rs1137070. The distribution analysis of polymorphism rs1799836 in the MAOB gene and all studied polymorphisms in the MAOA gene in females failed to show any significant results. GTC haplotype (for rs3027407, rs909525, rs1137070) in MAOA polymorphisms was more frequent in victims of complex suicide compared to that in controls and victims of simple suicide. Compared to victims of complex suicide, male victims of simple suicide were more often carriers of MAOA alleles that are, according to literature, associated with higher levels of impulsivity and anger. These differences in SNP distribution could serve as an additional method of differentiating between victims of complex and victims of simple suicide. Further studies including psychological autopsies should be carried out in order to identify personality traits and behavioural differences among distinct groups of suicide victims.

Collagen type III and elastin genes polymorphism and the risk of nonsyndromic striae.

Striae have been reported to be one of the most common skin lesions and a commonly encountered esthetic problem. The aim of this research was to examine elastin gene polymorphism (rs7787362, ELN) and collagen type III alpha 1 polymorphism (rs1800255, COL3A1) among polish woman population with SD in comparison with women without the lesions and to verify these polymorphisms as risk factors for SD. Seventy female students (35 with striae (the mean age 23.9years, SD 1.2years) and 35 without these lesions (22.9years, SD 1.7years)) were included in the study. The subjects were asked to fill out a questionnaire including questions concerning risk factors for SD and had a cheek swabbed for cells for DNA isolation. Analysis of polymorphisms of elastin gene (rs7787362) and COL3A1 gene (rs1800255) showed that women with SD and without these lesions did not differ in these aspects. Polymorphism rs7787362 was also analyzed in relation to SD in different locations, and showed no differences. In conclusion, we found that there are some clinical factors that reduced the risk of SD: history of intended weight loss, negative family history of SD, and lower BMI. Gene polymorphisms analysis in patients with SD may help to establish the etiology of these lesions and to target the therapy. Analysis of polymorphisms of elastin gene (rs7787362) did not show differences in allele distribution between women with and without SD. Polymorphisms of COL3A1 gene (rs1800255) also did not differ between the examined groups.

VEGF-A gene polymorphisms and responses to intravitreal ranibizumab treatment in patients with diabetic macular edema

To investigate the association between VEGF gene polymorphisms and the responses to treatment with intravitreal ranibizumab (IVR) in patients with diabetic macular edema (DME). This prospective study, conducted at the Kutahya Dumlupinar University Faculty of Medicine, included 95 patients with DME that were treated with IVR and 32 patients without DME despite proliferative diabetic retinopathy (PDR). The participants were divided into three groups: DME with non-proliferative diabetic retinopathy, DME with PDR, and PDR without DME; patients with DME who were treated with IVR were further divided into two groups based on their response to the treatment. Each patient was genotyped for five single nucleotide variations (SNVs) in VEGF-A: rs2010963, rs2146323, rs10434, rs833069, and rs6921438. There was a statistically significant difference in allelic distribution of VEGF-A rs833069 polymorphism in relation to the severity of diabetic retinopathy (DRP) (p=0.031). The allelic distribution of VEGF-A rs2146323 polymorphism tended to be associated with the severity of DRP (p=0.069). There were no statistically significant differences in the allelic distribution of the studied five SNVs in DME patients regarding the patients' responses to IVR therapy. There is no association between the studied VEGF-A SNVs and the responses to IVR therapy in DME. However, the VEGF-A rs833069 gene polymorphism has a clear association with the severity of diabetic retinopathy.