Difference In Genotype Distribution Research Articles

Evaluation of the interaction between insecticide resistance-associated genes and malaria transmission in Anopheles gambiae sensu lato in central C\xf4te d\u2019Ivoire

BackgroundThere is evidence that the knockdown resistance gene (Kdr) L1014F and acetylcholinesterase-1 gene (Ace-1R) G119S mutations involved in pyrethroid and carbamate resistance in Anopheles gambiae influence malaria transmission in sub-Saharan Africa. This is likely due to changes in the behaviour, life history and vector competence and capacity of An. gambiae. In the present study, performed as part of a two-arm cluster randomized controlled trial evaluating the impact of household screening plus a novel insecticide delivery system (In2Care Eave Tubes), we investigated the distribution of insecticide target site mutations and their association with infection status in wild An. gambiae sensu lato (s.l.) populations.MethodsMosquitoes were captured in 40 villages around Bouaké by human landing catch from May 2017 to April 2019. Randomly selected samples of An. gambiae s.l. that were infected or not infected with Plasmodium sp. were identified to species and then genotyped for Kdr L1014F and Ace-1R G119S mutations using quantitative polymerase chain reaction assays. The frequencies of the two alleles were compared between Anopheles coluzzii and Anopheles gambiae and then between infected and uninfected groups for each species.ResultsThe presence of An. gambiae (49%) and An. coluzzii (51%) was confirmed in Bouaké. Individuals of both species infected with Plasmodium parasites were found. Over the study period, the average frequency of the Kdr L1014F and Ace-1R G119S mutations did not vary significantly between study arms. However, the frequencies of the Kdr L1014F and Ace-1R G119S resistance alleles were significantly higher in An. gambiae than in An. coluzzii [odds ratio (95% confidence interval): 59.64 (30.81–131.63) for Kdr, and 2.79 (2.17–3.60) for Ace-1R]. For both species, there were no significant differences in Kdr L1014F or Ace-1R G119S genotypic and allelic frequency distributions between infected and uninfected specimens (P > 0.05).ConclusionsEither alone or in combination, Kdr L1014F and Ace-1R G119S showed no significant association with Plasmodium infection in wild An. gambiae and An. coluzzii, demonstrating the similar competence of these species for Plasmodium transmission in Bouaké. Additional factors including behavioural and environmental ones that influence vector competence in natural populations, and those other than allele measurements (metabolic resistance factors) that contribute to resistance, should be considered when establishing the existence of a link between insecticide resistance and vector competence.Graphical

Molecular epidemiology of hepatitis B virus genotypes and subgenotypes in ethnic minority populations, Yunnan province, China.

The aim of our study was to determine the distribution of hepatitis B virus (HBV) genotypes and subgenotypes in ethnic minorities in Yunnan province to provide evidence supporting the theoretical basis for hepatitis B prevention and control. We obtained serum samples and demographic data from 765 individuals reported by Yunnan province who had either acute or chronic HBV infection and were from one of 20 ethnic minority populations: Achang, Bai, Brown, Tibetan, Dai, Deang, Dulong, Hani, Hui, Jingpo, Lahu, Yi, Lisu Miao, Naxi, Nu, Pumi, Wa, Yao, or Zhuang people. We sequenced the HBV DNA and determined the genotypes and subgenotypes of the isolated HBVs. We mapped the genotype and subgenotype distribution by ethnic minority population and conducted descriptive analyses. There were four genotypes among the 20 ethnic groups: genotype B (21.3% of samples), C (76.6%), D (1.8%) and I (0.3%). The most common subgenotype was C1. There were no genotype differences by gender (P = 0.954) or age (P = 0.274), but there were differences by region (P < 0.001). There were differences in genotype distribution (P < 0.001) and subgenotype distribution (P = 0.011) by ethnic group. Genotype D was most prominent in Tibet and most HBV isolates were C/D recombinant viruses. The only two genotype I virus isolates were in Zhuang people. Susceptibility and geographic patterns may influence HBV prevalence in different ethnic populations, but additional research is needed for such a determination.

Association of Neurotensin Receptor 1 Gene Polymorphisms With Defense Mechanisms in Healthy Chinese.

Aims: In the central nerve system, neurotensin (NT), and neurotensin receptor 1 (NTR1) modulate the dopamine system. Gene variations in the dopamine system have been demonstrated to influence certain defense mechanisms, but no studies have investigated possible effect of NTR1 gene polymorphisms in the biological determination of these defenses. The present study therefore examined this link.Methods: In 412 healthy Han Chinese, single nucleotide polymorphisms rs6090453C/G, rs6011914C/G, and rs2427422A/G of the NTR1 gene were genotyped, and the defense mechanisms were measured by the self-reporting Defense Style Questionnaire 88.Results: Significant male-specific differences in the projective identification among the rs6090453 genotypes (p = 0.003); in the intermediate defense, reaction formation, and projective identification among the rs6011914 genotypes (p = 0.011, 0.010, and 0.011, respectively); and in the projective identification among the rs2427422 genotypes (p = 0.005) were found when the level of significance was adjusted by the Bonferroni correction. There was no significant difference in any of the defense scores among genotypes of any single nucleotide polymorphism in the total cohort or female subjects (all p > 0.017). The distributions of genotypes between the low and high score subgroups showed significant differences in the rs2427422 genotype distributions for help-rejecting complaining, regression, and projective identification (p = 0.010, 0.022, and 0.044, respectively). Significant differences were found between males and females in 10 defense mechanisms (all P < 0.05).Conclusions: The gene variations in the NTR1 polymorphisms were involved in the biological mechanisms of intermediate defense mechanisms, and this effect was influenced by sex.

Research on the relationship between V444A mutation of ABCB11 gene and primary intrahepatic stone

Objective: To investigate the relationship between V444A mutation of the ABCB11 gene and primary intrahepatic stone (PIS). Methods: A total of 164 patients (including 91 males and 73 females, with an average age of (46.0±13.0) years) with PIS and 164 healthy (including 99 males and 65 females, with an average age of (43.8±16.7) years) volunteers were enrolled in this case-control study between October 2017 and June 2019. TaqMan-MGB was used for detecting the V444A polymorphism site of the ABCB11 gene. All the genotypes and allele frequencies were calculated. Pearson chi-squared test was performed to detect the differences in allele and genotype distribution between the two groups. Logistic regression analysis was used to identify genotypes associated with PIS. Results: There was no significant difference in age and gender between the two groups(both P>0.05). The distributions of V444A allele and genotype accorded with Hardy-Weinberg equilibrium law (P=0.161), which indicated that the selected control group represented statistically acceptable sample. Two alleles of T and C, and three genotypes of TT, TC and CC were detected in the locus of V444A. The T and C allele frequencies in the PIS group and the control group were 28.4% vs 35.4%, and 71.6% vs 64.6%, respectively. The frequencies of the T and C alleles were not different between the two groups (P=0.054). The frequencies of TT, TC and CC genotypes in the two groups were 5.5%, 45.7%, 48.8%, and 14.6%, 41.5%, 43.9%, respectively, with significant difference between the two groups (P=0.023). Logistic regression analysis revealed the V444A polymorphism (TC heterozygous mutation) was associated with PIS. Conclusion: ABCB11 gene polymorphism at the site of V444A may be related to the susceptibility of PIS.

MicroRNA146a gene polymorphism in patients with rheumatoid arthritis and the relevant value with disease activity and extra-articular manifestations

Aim of the workTo analyze the relationship between miRNA-146a rs2910164 and rheumatoid arthritis (RA) susceptibility and clarifying its association with disease activity and extra-articular involvement. Patients and methodsThe study enrolled 50 RA patients and 40 controls. DNA extraction from whole blood was done. Genotyping was performed by real-time polymerase chain reaction. The selected single nucleotide polymorphism was rs2910164 in the miRNA-146a gene. Genotyping was performed on genomic DNA samples by allelic discrimination assay. Disease activity score (DAS28) and health assessment questionnaire-disability index (HAQ-DI) were assessed. ResultsThe mean age of patients was 44.8 ± 9.9 years while age at onset was 37.2 ± 9.8 years. Female:male was 5.3 vs 1. Females had significantly higher DAS28, visual analogue scale and rheumatoid factor (RF) than males (p = 0.04, p = 0.009, p = 0.03). The frequency of GC genotype was more in both males and females (62.5 vs 47.6%). GC genotype and G allele were the most frequent in patients. No significant difference in the frequency distribution of genotypes and alleles was observed between patients and controls. There was a significant difference in the number of swollen joints (p = 0.04) and sicca symptoms (p = 0.01) being higher in those with CC genotype with a tendency of increased DAS28, HAQ-DI, deformities and rheumatoid nodules with CC genotype and interstitial pulmonary fibrosis and RF with GG genotype. ConclusionsCC genotype was associated with sicca symptoms and swollen joints, deformities, disease activity and functional disability. miRNA-146a may be a potential biomarker for extra-articular manifestations of RA that need more attention and warrant aggressive therapy.

Genetic polymorphisms in the miR-372 (rs12983273) and LncRNA HULC (rs7763881) genes and susceptibility to Hepatitis B virus (HBV) infection.

MicroRNAs (miRNAs) and Long non-coding RNAs (lncRNAs) are two major types of non-coding RNAs (ncRNAs) with regulatory roles. The initiation and progression of numerous diseases have been linked to genetic variation in miRNAs and lncRNAs. Many diseases, including hepatitis infection, are thought to be regulated by miRNA-LncRNA interactions. In this study, Single nucleotide polymorphisms (SNPs) in miR-372 (rs28461391 C/T) and HULC (rs7763881 A/C) were believed to play a role in HBV infection risk. Using the Polymerase chain reaction sequence-specific primer technique (PCR-SSP), 100 HBV patients and 100 healthy controls were genotyped for SNPs rs28461391 in miR-372 and rs7763881 in HULC. There was no significant difference in miR-372 rs12983273 genotype distribution between controls and HBV patients, according to our findings. On the other hand, there was a significant increase in HULC rs7763881 CC genotype (P < 0.05) coincides with a significant decrease in AC genotype distribution (P < 0.05) in HBV patients as compared to controls. Our results showed that the AA genotype is protective for HBV infection (OR 0.3; CI 0.13-9.07) while the CC genotype is associated with an increased risk of HBV infection (OR 3.43; CI 1.3-9.07). Our results suggest that HULC rs7763881 A/C might be a biomarker for HBV susceptibility. Larger sample studies are needed to confirm our preliminary data. To the best of our knowledge, the present study was the first to investigate the relevance of miR-372 (rs28461391 C/T) and HULC (rs7763881 A/C) gene polymorphisms to the risk of HBV infection in the Egyptian population.

Evaluation of the Association of COMT Rs4680 Polymorphism with Swimmers' Competitive Performance.

Swimmers’ competitive performance is a result of complicated interactions between physiological, biochemical, physical and psychological factors, all of which are strongly affected by water. Recently, great attention has been paid to the role of genetic factors such as the catechol-O-methyltransferase gene (COMT) influencing motivation, emotions, stress tolerance, self-control, sleep regulation, pain processing and perception, addictive behaviour and neurodegeneration, which may underlie differences in achieving remarkable results in sports competition. Thus, this study was performed to investigate the association between the COMT Val158Met (rs4680) polymorphism and athletic performance in Caucasian swimmers. A total of 225 swimmers (171 short distance (SDS) and 54 long distance swimmers (LDS)) of national or international competitive standard and 379 unrelated sedentary controls were genotyped using real-time polymerase chain reaction (real-time PCR). We found no significant differences in genotypic or allelic distributions between (1) male and female athletes; (2) SDS and LDS; (3) all athletes and sedentary controls (under codominant, dominant, recessive, and overdominant genetic models). No association was found between the COMT rs4680 polymorphism and elite swimming athlete status of the studied population. However, more replication studies are needed.

Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with functional activity and oxidative modification of alpha-1-antitrypsin in COPD patients

ObjectiveChronic obstructive pulmonary disease (COPD) is multi–factorial disorder which results from environmental influences and genetic factors. We aimed to investigate whether methionine sulfoxide reductase A (MSRA) rs10903323 gene polymorphism is associated with COPD development and severity in Serbian adult population. MethodsThe study included 155 patients with COPD and 134 healthy volunteers. Genotyping was determined performing home-made polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The difference between the inhibitory activities of normal and oxidized Alpha-1-Antitrypsin (A1AT) against elastase and trypsin was used for determination of Oxidized Alpha-1-Antitrypsin (OxyA1AT) (expressed as % and g/L). Functional activity of A1AT was presented as a specific inhibitor activity to elastase (SIA-Elastase, kU/g). ResultsFrequencies of the genotypes AA, AG and GG were 80.0%, 20.0%, 0% in COPD patients and 80.5%, 18.5% and 1.5% in the control group, and there was no significant difference in genotype or allele distributions between groups. Serum level of A1AT (g/L) and OxyA1AT was significantly higher in COPD patients than in the control group, but functional activity of A1AT (SIA-Elastase) was significantly lower in COPD patients than in the control group. In COPD group, increased level of OxyA1AT was present in G allele carriers who were smokers relative to G allele carriers who were not smokers. In the smoker group of patients with severe and very severe COPD (GOLD3+4), significant increase in OxyA1AT level was present in G allele carriers compared to AA homozygotes. ConclusionThese findings suggest that MSRA rs10903323 gene polymorphism is probably not a risk for COPD by itself but could represent a COPD modifier, since minor, G allele, is associated with an increased level of oxidized A1AT, indicating impaired ability of MSRA to repair oxidized A1AT in COPD-smokers, and in severe form of COPD.

Association of TNFAIP3 gene polymorphism (rs5029939) with susceptibility and clinical phenotype of systemic lupus erythematosus.

Objectives This study aims to investigate the association of the tumor necrosis factor-alpha inducible protein 3 (TNFAIP3) (rs5029939) gene single nucleotide polymorphism (SNP) with the risk of systemic lupus erythematosus (SLE) and its clinical manifestations in a cohort of SLE patients.Patients and methods This study included a total of 180 participants (18 males, 72 females; mean age: 30.9±10.1 years; range 17 to 59 years) including 90 SLE patients and 90 healthy controls between March 2017 and February 2020. The TNFAIP3 rs5029939 gene polymorphism was identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in all participants.Results There was a significant difference in genotype distribution of the TNFAIP3 rs5029939 SNP between SLE patients and healthy controls, where CG genotype was more common in SLE patients (53.3%) than controls (11.1%) (p=0.001). We found a significant difference in G allele frequency of TNFAIP3 (rs5029939) (37.8% with SLE vs. 5.6% with controls, p=0.001). Genotype CG was significantly associated with lupus nephritis and neuropsychiatric manifestations (p<0.05). Although the response to treatment was numerically higher with the genotype CC, it did not reach statistical significance (p=0.4).Conclusion Our study suggests that TNFAIP3 rs5029939 gene polymorphism is associated with SLE susceptibility and may have an impact on its clinical phenotype. As such association differs among populations of diverse ethnic backgrounds, larger genome-wide association studies are warranted to further elucidate genetic associations.

LTA4H Prevalence and Mortality in Adult Zambians with Tuberculous Meningitis.

We conducted a prospective cohort study to determine the prevalence of leukotriene A4 hydrolase (LTA4H) polymorphisms in Zambian adults with tuberculous meningitis (TBM) and its association with mortality. We completed genotype testing on 101 definite cases of TBM and 119 consecutive non-TBM controls. The distribution of genotypes among TBM patients was as follows: C/C (0.83), C/T (0.14), T/T (0.03). There was no significant difference in genotype distribution between TBM and non-TBM patients. We found no relationship between LTA4H polymorphism and survival. Prospective studies are needed to determine the benefit of adjuvant steroids in TBM based upon population LTA4H genotype. ANN NEUROL 2021;90:994-998.

Leptin Receptor (rs1137101) and Brain-Derived Neurotrophic Factor (rs925946) Gene Variants Are Associated with Obesity in the Early- but Not in the Late-Onset Population of Hungarian Psoriatic Patients.

Background: Psoriatic patients have considerably higher odds of being obese compared with the general population; however, the exact pathophysiological link between psoriasis and obesity needs to be elucidated. Methods: To investigate the association of psoriasis with established obesity-related gene variants, we conducted a population-based case-control study including 3541 subjects (574 psoriasis cases and 2967 controls from the general Hungarian population). Genotyping of 20 SNPs at ADIPOQ, BDNF, FTO, GNPDA2, LEPR, MC4R, NEGR1, NPY, PPARG, TMEM18, and UCP2 were determined, and differences in genotype and allele distributions were investigated. Multiple logistic regression analyses were implemented. Results: Analysis revealed an association between the G allele of the rs1137101 polymorphism (LEPR gene) and obesity risk (OR: 3.30 (1.45; 7.50), p = 0.004) in the early-onset group of psoriatic patients. Furthermore, the T allele of rs925946 polymorphism (BDNF gene) was also associated with increased risk of obesity in early-onset psoriasis (OR: 2.26 (1.24; 4.14), p = 0.008). Conclusions: Our results suggest that in psoriatic patients, there are prominent differences in the causes of obesity that should be accounted for, including not only environmental factors but also patient characteristics, such as the time of disease onset as well as genetic factors.

Coronary artery disease association with serum concentration and genetic variation of MMP-9 in Ukrainian population

Abstract Introduction Coronary artery disease (CAD) is one of the main cause of death in European countries. The mortality associated with CAD has been rising for the past 30 years in Central and Easten Europe (including Ukraine). It is known that atherosclerosis is the primary risk factor of CAD development and Matrix metalloproteinase-9 (MMP-9) is involved in all stages of atherosclerosis and thus may contribute to CAD aggravation. It is very important to find specific mechanisms of atherosclerosis progression, the impact of genetic and external factors which influence on the development of CAD in different populations. Therefore, the aim of this study was to investigate the influence of MMP-9 concentration and functional rs17576 single nucleotide polymorphism (SNP) on risk of CAD development in Ukrainian population. Materials and methods In our study 128 patients were recruited. All of them we divided into three groups: 1 - with angiogrphically normal (intact) coronary arteries; 2 - patients with acute coronary syndrome (ACS) and 3 - with chronic coronary syndrome (CCS). The study protocol was approved by the Institutioal Ethics Committee and each participant was required to provide a writing informed consent. We recorded clinical data, biochemical analysis, performed electrocardiogram, coronary angiography and echocardiography. Blood for detection of MMP-9 and rs 17567 MMp-9 polymorphism was draw under standardized conditions before coronary angiography. Levels of MMP-9 were assessed using commercial ELISA immunoassay following manufacturer's instruction. The genotyping for MMP-9 rs17567-single nucleotide polymorphism was done by Real-time PCR. All statistical calculations were done using Statistical Package for the Social Sciences software. Results The results of analysis of association between MMP-9 rs17576 and CAD development demonstrate a weak link with borderline significance between MMP-9 concentration and ACS presence both before (Pc=0.026; ORc=1.003, 95% CI: 1–1.006) and after the adjustment for covariates (Pa=0.04; ORa=1.003, 95% CI: 1–1.006). In contrast, no significant association was detected for CCS group (Pa&amp;gt;0.05). There were no statistically significant differences in genotype and allele frequencies in compared groups (P&amp;gt;0.05) and association between MMP-9 serum concentration and MI occurrence. But we found the statistically significant differences in genotypes distribution (P=0.025) while the alleles distribution was similar (P&amp;gt;0.05) among compared groups. Additionally, AG-carriers had the lower risk of MI development in crude (Pc=0.033; ORc=0.359, 95% CI: 0.14–0.922) and adjusted (Pa=0.023; ORa=0.299, 95% CI: 0.106–0.848) overdominant model of inheritance. Conclusion In the present research we have analyzed the link of MMP-9 serum concentration and MMP-9 rs17567-polymorphic variant with CAD development among Ukrainians. We found lower risk of MI occurrence for AG-carriers. Funding Acknowledgement Type of funding sources: None.

HSP70 functional gene polymorphism and haplotype as a genetic factor for type 2 diabetes mellitus

Oxidative stress is a major cause underlying the development of Type 2 Diabetes Mellitus (T2DM). The heat shock protein 70 (HSP70) is a redox sensor for intracellular oxidative stress. The present study was aimed to understand the association of HSPA1L (HSP70-hom) rs2075800 and HSPA1B (HSP70-2) rs6457452 gene polymorphisms and haplotype with susceptibility to T2DM. In this case-control study, 200 T2DM patients and 200 healthy people were genotyped for HSPA1L rs2075800 and HSPA1B rs6457452 polymorphisms by Tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) method. The HSPA1B rs6457452 CT (OR = 0.52, 95%CI: 0.33–0.81, P = 0.004) and TT (OR = 0.05, 95%CI: 0.07–0.43, P = 0.005) genotypes were associated with decreased risk of T2DM. Moreover, the T allele was detected as a protective genetic factor against T2DM (OR = 0.43, 95%CI: 0.29–0.63, P < 0.001). We didn't find any significant differences in genotype and allele distributions between T2DM patients and controls for HSPA1L rs2075800 polymorphism. Haplotype analysis showed significant results for all haplotype windows except AC (rs6457452/rs2075800) haplotype. Haplotype GT (OR = 0.554; 95%CI = 0.332–0.924; p = 0.022) and AT (OR = 0.388; 95%CI = 0.230–0.654; p = 0.0002) showed highly significant association with decreased risk of T2DM. Increased risk was observed in haplotype GC (OR = 1.505; 95%CI = 1.132–1.999; p = 0.004). In conclusion, we conducted for the first time, that these polymorphism and haplotype are associated with T2DM in an Iranian population.

Matrix Metalloproteinase 2 Is Associated With Secondary Caries Independent From the Restorative Material

Certain patients, despite receiving proper treatment, still show higher failure rates of restorative dental treatments. The aim of this work was to test if MMP2 and MMP3 alleles are overrepresented in individuals with secondary caries. A total of 1,089 individuals from the University of Pittsburgh School of Dental Medicine Dental Registry and DNA Repository project were selected for this study. From this total, 341 individuals were selected for having a record of secondary caries in any type of restoration and were matched with 748 individuals by sex, age, ethnicity, and restorative work in the same teeth that did not fail. Genomic DNA extracted from saliva was used to obtain genotypes in five markers of MMP2 and MMP3 using TaqMan chemistry and end-point analysis. Chi-square was used to test if differences in allele and genotype distributions were statistically different at an alpha of 0.05. The less common allele and homozygote genotype of MMP2 rs9923304 were less commonly found among individuals with secondary caries. The less common allele of MMP2 rs2287074 was also less frequent among individuals with secondary caries. These results provide statistical evidence for the role of MMP2 in failure of restorations due to secondary caries. We can conclude that MMP2 variation impacts the risk of having secondary caries, independent of the restorative material.

Association between genetic variations at 8q24 and prostate cancer risk in Mexican Men.

Variants of 8q24 locus have been associated with prostate cancer (PCa) susceptibility. This study aims to analyze the genetic basis of PCa susceptibility in Mexican men by analyzing SNPs in the 8q24 locus for the first time. A case-control study was performed in 875 men recruited from the Mexican Social Security Institute, 326 patients with PCa, and 549 non-PCa patients (88 with benign prostatic hyperplasia BPH and 461 healthy controls). The 8q24 locus SNPs: rs16901979, rs16983267, rs1447295, and rs7837328 were genotyped by allelic discrimination assays using TaqMan probes. Statistical analysis was performed using Epi Info statistical 7.0 and SNPstats softwares. All genotype frequencies were in Hardy-Weinberg Equilibrium. No differences were observed in genotype distribution between PCa and non-PCa patients for rs6983267. Under different inheritance models, the rs16901979, rs1447295, and rs7837328 SNPs were associated with PCa (OR = 2.8, 1.8, and 1.72, respectively; Pc < 0.001) when comparing PCa patients against controls. This association remains between PCa and BPH patients under different models (OR = 8.5, 2.2, and 1.9, respectively; Pc < 0.001). There were no significant differences in allele and genotype distribution among BPH patients and controls. The combined effect of the alleles CGAA for the SNPs rs16901979, rs6983267, rs1447295, and rs7837328 showed significant differences between PCa patients and controls (OR = 2.9, 95% CI = 1.48-5.83, Pc = 0.008). Four 8q24 variants were not associated with D'Amico score, age at diagnosis, and bone metastases. Our study provides the first confirmation that variants rs16901979, rs1447295, and 7837328 at 8q24 locus are associated with PCa susceptibility in Mexican men.

Potential protective role of a NOD2 polymorphism in the susceptibility to multiple sclerosis is not associated with interferon therapy.

Pattern recognition receptors, such as specific nucleotide-binding oligomerization domain protein 2, and their polymorphisms may be involved in the pathogenesis of multiple sclerosis (MS). They may also play a role in the formation of neutralizing antibodies against interferon-β (INF-β), and may exhibit lowered efficacy. Identification of these polymorphisms may be useful for early identification of potential non-responders and to allow for modification of treatment regimens earlier. The differences in genotype distribution and allele frequency of the rs3135499 and rs2066842 NOD2 polymorphisms between patients with MS and healthy controls were analysed in the present study. The group of patients were divided into responders and non-responders to INF-β therapy to evaluate the association of both polymorphisms with response to therapy. No differences in the genotype frequencies between the responder and non-responder groups were observed. However, a statistically significant difference in genotype frequencies of TT homozygotes for rs2066842 between patients with MS and healthy controls was observed (χ2=11.8; P=0.003). A recessive genotype model and allele distribution in rs2066842 suggest that the genotype TT and allele T itself are protective against MS. The odds ratio of 0.12 represents an 8.33x lower risk for MS if an individual has a TT genotype. The significantly lower incidence of the TT genotype of rs2066842 in patients with MS suggests that the TT genotype and T allele may be a protective genetic factor against MS.

Association Study of Polymorphisms in Neuronal Nicotinic Acetylcholine Receptor Subunit Genes With Schizophrenia in the Han Chinese Population.

ObjectiveTo investigate the relation between nicotinic acetylcholine receptor subunit (nAChR) genes and schizophrenia, and the relation between tag single nucleotide polymorphism (rs1317286, rs1044396, rs6494212, rs16969968, and rs684513) and schizophrenia in Han Chinese people. MethodsThe protein-protein interaction (PPI) network among nAChR protein and 350 proteins encoded by schizophrenia-related susceptibility genes was constructed through the String database to explore whether nAChR genes were associated with schizophrenia in these known databases. Then, five single nucleotide polymorphisms (SNPs) of CHRNA3 (rs1317286), CHRNA4 (rs1044396), CHRNA7 (rs6494212), and CHRNA5 (rs16969968, rs684513) were analyzed in a sample of 1,035 schizophrenic patients and 816 healthy controls. The interaction between the markers was analyzed using multifactor dimensionality reduction (MDR) software. Power analysis was performed using the Quanto program. ResultsThere are no significant differences in genotype or allele distribution were identified between the patients and controls (p>0.05). The haplotypes constructed by four markers rs1317286, rs6494212, rs16969968, and rs684513 were not associated with schizophrenia either. However, a significant association between models made of rs1317286, rs1044396, rs6494212, and rs684513 and schizophrenia was revealed in interaction analysis (p<0.05). ConclusionThe nAChR protein may have effects on the development of schizophrenia through the interaction with proteins encoded by schizophrenia-related susceptibility genes, but no relation was found between selected polymorphisms and schizophrenia in the collected Han Chinese people. However, interaction analysis suggested four-SNP model has an important effect on schizophrenia.

Alliance of Matrix Metalloproteinase-9 Promoter-1562C/T Polymorphism and Metalloproteinase-9 Saliva Concentration of Iraqi Patients with Chronic Periodontitis

Matrix metalloproteinases (MMPs) are key enzymes responsible for matrix degradation, derived frompolymorphonuclear leukocytes, during the early stages of periodontitis. There is plenty of evidencefor the role of matrix metalloproteinases in the destructive processes of periodontal disease as a viabletarget in early diagnosis and chemotherapeutic approach. The aim of this study was to determine thelevels of salivary matrix metalloproteinase-9 (MMP-9) in patients with periodontitis and healthycontrols and the role of gene polymorphisms in the aetiology of the disease. Levels of MMP-9 insaliva was determined by enzyme linked immune sorbent assay (ELISA) technique in healthy subjectswithout any periodontal disease (n = 45) and in the patients with diagnosed periodontitis (n = 45).Gene Amplification, gel electrophoresis and genotyping were also carried out on MMP-9 gene. TheMMP-9-1562C/T appeared in three genotypes: CC, CT and TT, allele specific gene polymorphism wasamplified by PCR technique. The distribution of different genotypes in patients and controls for each ofMMP-9-1562C/T polymorphism was in a good accordance with Hardy-Weinberg equilibrium (HWE).Genotypes in both dominant and recessive models were non-significantly associated with periodontitis.Significantly higher salivary MMP-9 was observed in cases of periodontitis compared to healthy adults(p = 0.043). Salivary MMP-9 may serve as a biomarker of periodontal disease monitoring and aid inthe early detection of periodontitis.

A novel 4-bp insertion within the goat CFAP43 gene and its association with litter size

• A 4-bp deletion ( CFAP43-P2 ) and a 4-bp insertion ( CFAP43-P3 ) were identified within the goat CFAP43 gene. • CFAP43 -P3 was significantly associated with goat litter size ( P = 0.001). • DD genotype of CFAP43 -P3 exhibited more superior litter size trait compared with ID. Cilia and flagella associated protein 43 ( CFAP43 ) gene, also known as WDR96 , is widely expressed in gonadal tissues. The mutation of this gene is the cause of multiple morphological abnormalities and is related to male and female infertility. This work aimed to further clarify the correlation between novel mutation within CFAP43 gene and litter size in Shaanbei white cashmere goat population. In this study, we detected three putative InDel variants within CFAP43 gene, and ANOVA analysis indicated that a novel 4-bp insertion mutation in intron 7 was significantly associated with goat litter size ( P = 0.001). This locus contained three genotypes and was of medium genetic diversity. Meanwhile, DD genotype exhibited more superior litter size trait than ID carrier ( P < 0.05). The chi-square test showed there was a significant difference in genotype distribution between the mothers of single lamb and the mothers of multi-lamb ( P = 0.006). In summary, our findings suggested the 4-bp insertion within CFAP43 gene could act as a molecular marker to contribute to improving goat litter size in the breeding program.

Inclusion of ALKBH5 as a candidate gene for the susceptibility of autoimmune thyroid disease

PurposeRNA demethylase AlkB homolog 5 (ALKBH5) gene is pivotal in N6-methyladenosine (m6A) modification. Therefore, this study aimed to explore the potential relationship between polymorphisms of ALKBH5 gene and the development of autoimmune thyroid disease (AITD). Material and methodsA case-control study of 979 AITD patients, including 620 Graves' disease (GD) and 359 Hashimoto's thyroiditis (HT), and 732 normal controls of the Chinese Han population was performed using high-throughput sequencing (HiSeq) genotyping method for detecting 5 variants in ALKBH5 gene (rs12936694, rs2124370, rs4925144, rs8068517, and rs9913266). In addition, the associations between ALKBH5 single nucleotide polymorphisms (SNPs) and clinical phenotypes of AITD were investigated. ResultsCompared to normal controls, rs9913266 displayed significant differences in allele and genotype distributions in AITD and GD. rs12936694 also showed significantly different frequencies of alleles in AITD and GD. The link of these 2 loci polymorprhisms to AITD and GD also existed after adjusting for age and gender. When stratified by sex, the minor allele of rs9913266 was associated with the risk of female AITD and HT development before and after adjusting for age and gender. There was a significant association between rs8068517 locus and GD in females after adjusting for the confounders. Finally, we observed significant correlations of haplotypes CGACA and CAGCG to the susceptibility of AITD and GD. ConclusionsOur results provided evidence of association of polymorphisms in ALKBH5 gene with AITD, GD, and HT patients, and hence ALKBH5 might be the candidate gene for susceptibility to AITD.