TA Haplotype Research Articles

Association of c.+677 C>T (rs1801133) and c.+1298 A>C (rs1801131) MTHFR genetic variants with cardiometabolic and disease risk in systemic lupus erythematosus patients: A cross-sectional study.

Systemic lupus erythematosus (SLE) patients present a high prevalence of cardiometabolic risk, associated with worse clinical manifestations and mortality. Folate, an essential micronutrient that participates in vital immune cellular functions, could positively affect the cardiometabolic and disease risk in SLE, through the methylenetetrahydrofolate reductase (MTHFR) enzyme, which participates in the folate metabolism, where single nucleotide variants (SNVs) have been described as a potential genetic risk factor for SLE. The aim of this study was to determine the association of the c.+677C>T (rs1801133) and c.+1298 A>C (rs1801131) MTHFR genetic variants with cardiometabolic risk and clinical disease variables in SLE patients. A case-control study was conducted on 394 unrelated Mexican-mestizo women: 199 with SLE according to the 1997 SLE-ACR criteria and 196 control subjects (CS). Folic acid and homocysteine levels were evaluated by immunoassays. Genotyping of MTHFR genetic variants was carried out by allelic discrimination. No significant differences were found for folic acid (p = .15) and homocysteine serum levels (p = .59) between groups. According to the CC c.+677 MTHFR genotype, this was associated with low cardiovascular disease (CVD) risk by the Castelli index (OR = 0.42; p = .03) in SLE patients. The TC (OR = 1.3; p = .03) and the TA (OR = 1.6; p < .01) haplotypes from c.+677C>T plus c.+1298 MTHFR were associated with SLE risk, while the CC MTHFR haplotype (OR = 0.5; p = .01) was found as a non-risk factor for the disease. In conclusion, the TC and the TA MTHFR haplotypes are associated with disease risk; meanwhile, the CC c.+677 MTHFR genotype confers lower cardiometabolic risk in Mexican-mestizo SLE patients.

Study on the Association of XRCC1 Gene rs72484243 Polymorphisms with Increased Laryngeal Cancer Risk

Objective: To study the association of X-ray repair cross-complementing group 1 (XRCC1) gene polymorphisms with increased laryngeal cancer risk. Methods: A total of 120 individuals, comprising 60 patients with laryngeal squamous cell carcinoma (LSCC), and 60 healthy volunteers participated were selected. Blood samples were taken and analyzed, and 4 XRCC1 polymorphisms (rs145135970, rs1799780, rs25489, and rs72484243) were genotyped. Results: Gender, age, body mass index (BMI), and smoking habits were shown to be the high-risk factors for LSCC. Genotype and allele distributions for the 4 polymorphisms differed significantly between both groups (P &lt; 0.05). Furthermore, carriers with the rs72484243GTGT- allele exhibited an increased risk of LSCC relative to those who had the rs145135970 GTGTGTGTGTGTGT- allele, the rs1799780 G-A allele, or the rs25489 C-T allele, as determined by binary logistic regression analysis (OR = 2.74, 95% CI: 1.27–5.91, P = 0.01), after accounting for possible co-factors like sex, age, BMI, drinking and smoking behavior, and special diet requirements. In addition, a TA haplotype and a GTGTGTGTGTGTGTTG haplotype were linked to LSCC in Chinese populations in a haploid association study of 4 SNP loci in the XRCC1 gene (P = 0.05 OR = 1.36, 95% CI = 1.1228–1.6406). Conclusion: Genetic polymorphisms of the XRCC1 gene at the rs72484243 site were correlated with an elevated risk of LSCC among the Xinjiang population.

TLR4 Polymorphisms (T399I/D299G) Association with Schizophrenia and Bipolar Disorder in a Tunisian Population.

Immune dysregulation has been widely described in the pathophysiology of schizophrenia (SCZ) and bipolar disorder (BD). Particularly, TLR4-altered activation was proposed as one of the underlying processes of psychosis onset. Since TLR4 activation was altered by T399I and D299G polymorphisms, we hypothesized that those variants could present common genetic factors of SCZ and BD. A total of 293 healthy volunteers and 335 psychotic patients were genotyped using PCR-RFLP. Genotype, allele, and haplotype distribution between controls and patients were evaluated according to clinical parameters. Statistical analyses were adjusted by logistic regression. In dominant model, T399I CT + TT and allele frequency were significantly higher in controls compared to psychotic population (p = 0.004, p = 0.002, respectively), SCZ (p = 0.02, p = 0.01, respectively), and BD (p = 0.03, p = 0.02, respectively). Similarly, D299G AG + GG and allele frequency were significantly higher in controls compared to psychotic population (p = 0.04, p = 0.04, respectively) and SCZ (p = 0.04, p = 0.03, respectively). T399I CT + TT and T allele were overrepresented in controls compared to paranoid subgroup (Padjusted = 0.04, p = 0.04, respectively) and type I BD (p = 0.04). Moreover, T399I and D299G were less prevalent in SCZ late-onset age (p = 0.03, p = 0.02, respectively). TA haplotype was associated with protection from psychoses (p = 0.02) and particularly from schizophrenia (p = 0.04). In conclusion, TLR4 polymorphisms could present a preventive genetic background against psychoses onset in a Tunisian population. While T399I could be associated with protection against SCZ and BD, presenting an overlapping genetic factor between those psychoses, D299G was suggested to be associated with protection only from schizophrenia.

Single nucleotide polymorphisms of the SIF gene and their association with growth traits in swimming crab (Portunus trituberculatus)

The swimming crab (Portunus trituberculatus) is an economically important aquaculture species in China. Mining candidate single nucleotide polymorphisms (SNPs) and genes associated with growth traits of P. trituberculatus is of great importance for the genetic breeding of this species. Among the genes associated with growth traits, “protein still life, isoforms C/SIF type 2 (SIF)” is thought to be an important gene affecting animal growth and development. In the current study, we investigated the SIF gene from P. trituberculatus to better understand its biological function. The full-length cDNA of SIF was 6185 bp, with a 5208 bp open reading frame encoding 1735 amino acids. Homology analysis showed that SIF shared 90.07% identity with Procambarus clarkii and 40.25–86.95% with other species. Expression pattern analysis of SIF in fast- and slow-growing groups revealed a significantly higher expression level in the former than in the latter (P < 0.05). qPCR studies revealed the ubiquitous expression of SIF in seven tissues tested, but most abundantly in the heart compared with muscle, testis, ovary, seminal vesicle, gill, and hepatopancreas (P < 0.05). A total of 38 SNPs in the UTRs and exons of SIF were screened and genotyped in 184 individuals of swimming crabs by targeted resequencing. Association analysis showed that four SNPs were significantly associated with growth traits (full carapace width, carapace length, body height, and body weight; P < 0.05). Two SNPs out of the four SNPs were shaped as a haploblock containing three haplotypes (GC, TA, and TC), and the TA haplotype showed significantly higher growth traits than the GC haplotype. Overall, the results provided potential candidate genes and SNP markers for the genetic improvement of growth traits in P. trituberculatus breeding.

EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) POLYMORPHIC VARIATIONS (-216G/T & -191 C/A) POSE A HIGH RISK TO PATIENTS WITH MALIGNANT GLIOMA.

Malignant gliomas are the most frequent and lethal brain tumors. Their molecular aspects remain intangible but current studies have pointed to certain genetic polymorphic loci that pose the risk. The polymorphic sequence variations of the epidermal growth factor receptor gene (EGFR) pathway play a vital role in the glioma risk, and the EGFR variants (216G>T and 191C>A) are identified to affect the risk for the development of different tumors including glioma. To examine genetic variations of EGFR T rs712829 (216G/T) and rs712830 (191C>A) with respect to glioma risk. 129 confirmed glioma cases were genotyped against 180 malignancy-free healthy controls by polymerase chain reaction-restriction fragment length polymorphism technique (RFLP). The frequency of the TT homozygous variant of the EGFR -216 G/T genotype differed significantly between cases and controls (49.6% vs. 23.0%) (p < 0.0001). The EGFR -216 G>T allele 'T' was found significantly more frequently in cases (0.56 vs. 0.33 in controls; p < 0.0001). The EGFR -191C>A homozygous 'AA' genotype was implicated significantly more frequently in cases than in controls (p < 0.0001). The distribution of the 'A' variant allele was also more frequent in cases (41.9%) than in controls (14.0%) (0.55 vs. 0.30; p < 0.0001). TC and TA haplotypes showed varied frequency in cases and controls. EGFR -216 G>T and -191 C>A variants and haplotypes (TA and TC) of the EGFR gene are very strong risk factors in the development of glioma in the Kashmiri population.

Population analysis of the CLOCK rs3749474T-rs4864548A haplotype and its relationship with obesity.

It has been suggested that the rs3749474T/rs4864548A haplotype of the CLOCK gene increases the risk of obesity, but the population variability of these alleles and the haplotype is unknown. This research aims to determine the linkage between the rs3749474T and rs4864548A alleles from the database of 1000Genomes to confirm the existence of the TA haplotype polymorphisms of these alleles and their frequency in five macro populations. Linkage disequilibrium and haplotype frequencies for 2504 individuals from 26 populations were analyzed using the r statistic and Fisher's exact test. There is a high frequency of the TA haplotype in Latin America (44.8%), a high linkage disequilibrium (r2= 0.92) worldwide between these alleles, a high differentiation between macro populations, and a high homogeneity. The evidence warrants further studies on the association between this haplotype and the risk of obesity and overweight in Latin American populations.

Novel Haplotype in the HHEX Gene Promoter Associated with Body Length in Pigs.

The screening of important candidate genes and the identification of genetic markers are important for molecular selection in the pig industry. The hematopoietically expressed homeobox (HHEX) gene plays an important role in embryonic development and organogenesis; however, the genetic variation and expression pattern of the porcine HHEX gene remains to be clarified. In this study, semiquantitative RT-PCR and immunohistochemistry results showed the specific expression of the HHEX gene in porcine cartilage tissues. A novel haplotype consisting of two SNPs rs80901185 (T > C) and rs80934526 (A > G) was detected in the promoter region of the HHEX gene. The expression of the HHEX gene was significantly higher in Yorkshire pigs (TA haplotype) than in Wuzhishan pigs (CG haplotype), and a population analysis showed that this haplotype was significantly associated with body length. An analysis subsequently revealed that the -586 to -1 bp region of the HHEX gene promoter showed the highest activity. Furthermore, we found that the activity of the TA haplotype was significantly higher than that of the CG haplotype by changing the potential binding of transcription factors YY1 and HDAC2. In summary, we conclude that the porcine HHEX gene may contribute to the breeding of pigs for body length traits.

Genetic Association of VDR gene Apa1 and Taq1 Variants with Scleroderma in an Iranian Northeast Population.

Despite vigorous research efforts, the etiology of scleroderma (systemic sclerosis (SSc)) remains still unclear and both genetic and environmental factors clearly contribute to the pathogenesis of scleroderma. Reports of aberrant vitamin D status in scleroderma patients suggest a need for considering the genotype and allele frequencies of VDR gene polymorphisms. This case-control study aimed to investigate the possible association of two common polymorphisms of the VDR gene (ApaI, and TaqI) with susceptibility to scleroderma in an Iranian population. Using polymerase chain reaction and restriction fragment length polymorphism (PCRRFLP), ApaI and TaqI polymorphisms in the VDR region were genotyped in 51 patients with scleroderma and 50 healthy controls. Logistic regression analysis was performed to calculate the genotypes odds ratios (ORs) as a measure of association with the presence of scleroderma. Haplotype and linkage disequilibrium analyses were also performed on the detected genotypes. No significant differences were found for the allelic and genotype distributions of ApaI and TaqI polymorphisms between patients with scleroderma and healthy controls (p>0.05). In haplotype analysis, three haplotypes TA, CA, and TC, with a frequency greater than 1% were identified. However, none of them was associated with the risk of scleroderma. Our preliminary study showed no evidence of an association between ApaI and TaqI polymorphisms and scleroderma. As the association between VDR polymorphisms and autoimmune diseases varies across the different ethnic populations, further large cohort studies are necessary to confirm the results.

Novel Association of IGF2BP2 Gene Variants With Altered Risk of Breast Cancer and as Potential Molecular Biomarker of Triple Negative Breast Cancer

BackgroundSeveral studies documented that insulin-like growth factor-2 mRNA-binding protein 2 (IGF2BP2) contributes to carcinogenesis, and 1 report documented the association of IGF2BP2 rs4402960 with increased risk of breast cancer (BC). This study investigated the association of rs4402960 and rs1470579 IGF2BP2 variants with BC and triple negative BC (TNBC). Materials and MethodsThis case-control study included 488 BC patients comprising 130 TNBC and 358 non-TNBC patients, and 476 cancer-free controls. Genomic DNA was obtained from peripheral venous blood, and genotyping was done by allelic exclusion method on real-time PCR. ResultsThe rs440960, but not rs1470579, minor allele was significantly associated with BC, and significantly higher rs4402960 T/T genotype frequency was noted in BC patients than controls; the distribution of rs1470579 genotypes were comparable between BC patients and controls. In contrast, significantly lower rs1470579 minor allele frequency, and reduced rs1470579 A/C and C/C, and rs4402960 T/T genotype frequencies were seen in TNBC cases. Among TNBC cases, rs4402960 and rs1470579 correlated with menses pattern, histological type, breastfeeding, oral contraceptive use and hormonotherapy. Among non-TNBC patients, and rs1470579 correlated significantly with breast feeding, oral contraceptive use, hormonotherapy, and nodal status; rs4402960 also correlated with menses pattern. Two-locus (rs440960-rs1470579) haplotype analysis confirmed the positive association of TC, and negative association of GC and TA haplotypes with BC, while TC and GC haplotypes were negatively associated with TNBC. ConclusionWhereas rs440960 was positively associated with BC, both rs4402960 and rs1470579 were negatively associated with TNBC, suggesting potential diagnostic/prognostic role in BC and its complications.

Association of Genetic Variability in Selected Genes with Platelet Hyperaggregability and Arterial Thrombosis

Abstract Introduction: Inherited platelet hyperaggregability, so called “Sticky platelet syndrome” (SPS), is a prothrombotic platelet disorder. The syndrome contributes more often to arterial than venous thrombosis. The most common localization of arterial occlusion involves cerebral or coronary arteries. However, SPS may also lead to thrombosis in the atypical sites of the circulation. This qualitative platelet alteration causes platelet hyperaggregability after a very low concentration of platelet inducers – adenosine diphosphate (ADP) and/or epinephrine (EPI). The precise genetic background of the syndrome has not been defined. In the present study we aimed to determine the association between selected single nucleotide polymorphisms (SNPs) within genes for platelet endothelial aggregation receptor 1 (PEAR1) and murine retrovirus integration site 1 (MRVI1) and the risk for arterial thrombosis in patients with SPS. The products of these selected genes play an important role in platelet aggregation. Patients and methods: We examined 69 patients with SPS and a history of arterial thrombosis and 69 healthy blood donors who served as controls. SPS was confirmed by a light transmission aggregometry (LTA) according to the method and criteria described by Mammen and Bick. We assessed two SNPs within PEAR1 gene (rs12041331, rs1256888) and two SNPs within MRVI1 gene (rs1874445, rs7940646). Results: Selected PEAR1 and MRVI1 polymorphisms seem not to be a risk factor for the development of SPS as the syndrome with an arterial thrombosis phenotype. However, in the subgroup of SPS1 patients there was found a decreased frequency of the minor A allele of SNP rs12041331 in PEAR1 gene (borderline p value, p=0.061) that can be hypothesized as protective against arterial thrombosis. In the same SPS1 subgroup the haplotype TA in PEAR1 gene also showed a decreased frequency with a borderline insignificance (p=0.056). We can theorize also about its protective role in SPS1 patients. We did not confirm the protective effect of polymorphism (T/T of rs 12566888) in PEAR1 against arterial thrombosis in SPS patients and SPS subgroups. Conclusion: Our results support the idea that examined genetic variability of the selected SNPs in PEAR1 and MRVI1 genes is not associated with platelet hyperaggregability manifested as arterial thrombosis. The possible protective role of the minor A allele of SNP rs12041331 as well as a role of haplotype TA in PEAR1 gene related to the arterial thrombosis found in the subgroup of SPS1 patients needs to be verified in further research.

Association study of CLDN14 variations in patients with kidney stones.

Claudin-14 protein plays an essential role in regulating calcium ions in the kidney and ear. Two phenotypes, hearing loss and kidney stones, were reportedly associated with variations in the CLDN14 gene. This study aimed to understand CLDN14 mutations’ contribution to hearing loss and renal stone formation in a Pakistani cohort. We analyzed CLDN14 sequence variations in 100 patients, along with healthy individuals, to assess whether specific polymorphisms were associated with the disease. Also, we performed an in silico analysis using a mutation database and protein annotation. The rs219779’s genotype CT (p = 0.0020) and rs219780’s genotype AG (p = 0.0012) were significantly associated with kidney stones. We also found that a novel haplotype, “TA” associated with kidney stone formation, has moderate linkage disequilibrium. The TA haplotype was significantly correlated with a kidney stone risk formation of 3.76-fold (OR (CI 95%) = 3.76 (1.83–7.72)) and p = 0.0016 compared to other haplotypes. In silico analysis revealed that mutations associated with hearing loss were not correlated with renal stone formation but affected claudin-14 protein stability. We structurally mapped a novel TA haplotype of CLDN14 that, based on our analysis, likely contributes to the pathogenesis of renal stones.

Association of the ADCY9 gene and gene-environmental interaction with the susceptibility to childhood bronchial asthma

To study the association of the single nucleotide polymorphisms (SNPs) of the adenylyl cyclase IX (ADCY9) gene at rs1967309, rs2230739, rs2601814, rs2601825, rs2601796, and rs2283497 loci and gene-environment interaction with childhood bronchial asthma (asthma for short). A total of 123 children with asthma who attended the hospital from March 2019 to September 2021 were enrolled as the asthma group, among whom 84 (68.3%) had mild-to-moderate attacks and 39 (31.7%) had severe attacks. A total of 124 healthy children were enrolled as the control group. The association of the SNPs and haplotypes of the ADCY9 gene at the above 6 loci with the susceptibility to childhood asthma was evaluated. The method of generalized multifactor dimensionality reduction was used to analyze gene-environment interaction. Polymorphisms were observed for the ADCY9 gene at the above six loci in both the asthma and control groups, and there were significant differences in genotype and allele frequencies at the rs1967309 locus between the two groups (P<0.05). There was no significant difference in the distribution frequency of haplotypes TA and GG between the asthma and control groups (P>0.05). The generalized multifactor dimensionality reduction analysis showed interaction between rs1967309 locus and allergen contact (P<0.05), which increased the risk of asthma (OR=1.585, P<0.05). The rs1967309 locus of the ADCY9 gene is associated with the susceptibility to childhood asthma, and the locus and allergen contact have a synergistic effect on the development of asthma.

Association analysis of GAS5 polymorphisms and psoriasis

Psoriasis is a complex disorder with genetic background. Previous studies have reported the presence of some genetically-influenced factors for this disorder. In the current study, we genotyped rs2067079 and rs6790 polymorphisms of GAS5 lncRNA in Iranian patients with psoriasis and healthy controls. Genotype frequencies of rs2067079 and rs6790 were in accordance with the Hardy-Weinberg equilibrium both in cases and controls. Distributions of alleles/genotypes of rs2067079 and rs6790 polymorphisms were similar between patients with psoriasis and healthy controls. None of these SNPS were associated with risk of psoriasis in any inheritance model. We also appraised association between GAS5 haplotypes and risk of psoriasis. Frequencies of CG, TG, CA and TA haplotypes (rs2067079 and rs6790) were statistically similar between patients with psoriasis and healthy controls. Thus, mentioned polymorphisms are not associated with risk of psoriasis in Iranian population.

A Novel CYP2C-Haplotype Associated With Ultrarapid Metabolism of Escitalopram.

Escitalopram is one of the most commonly used antidepressant drugs but exhibits a substantial interindividual variation in clinical response. A key factor underlying response differences is the polymorphic nature of the CYP2C19 gene encoding the major enzyme responsible for escitalopram metabolism. Although pre-emptive CYP2C19 genotyping may improve escitalopram treatment outcome by dose individualization, much of the interindividual variability cannot be assigned to the currently known CYP2C19 gene variants. The aim of the present study was to search for novel CYP2C-haplotypes for better genetic prediction of escitalopram metabolism. First, the CYP2C18/CYP2C19 locus was sequenced from gDNA obtained from 24 patients previously genotyped as CYP2C19*1/*1 showing consistently low serum concentrations of escitalopram (<25nM/10mg). Three new haplotypes of the CYP2C locus (CYP2C:TG, CYP2C:TA, and CYP2C:CG) were here identified, and their functional roles were evaluated using gDNA from 875 previously genotyped escitalopram-treated patients. The CYP2C:CG and CYP2C:TA haplotypes had no significant impact on escitalopram concentration. Based on the estimated effects of the novel CYP2C-haplotypes on escitalopram exposure, the predicted serum concentrations of escitalopram in homozygous CYP2C:TG and CYP2C19*17 carriers were 24.8% and 17.3% lower compared with the baseline (CYP2C:CG and CYP2C:TA), respectively. In conclusion, a novel CYP2C-haplotype defined by rs2860840T and rs11188059G associated with ultrarapid metabolism of escitalopram was identified. Further studies should clarify the genetic basis for the enhanced escitalopram metabolism and the impact of the CYP2C:TG haplotype on the metabolism of other CYP2C19 substrates like omeprazole, voriconazole, and clopidogrel.

Identification of CXCL8c.105A>G and CXCL8c.210C>T polymorphism in Polish HF cattle

Background: Bovine chemokine C-X-C motif legend 8 (CXCL8) also known as interleukin 8 (IL8) is a chemotactic factor that attracts neutrophils, basophils, and T-cells, in response to an inflammatory stimulus. The aim of this study was to investigate the novel single nucleotide polymorphisms (SNPs) located at the promoter region of CXCL8 gene in Polish Holstein Friesian (HF) bulls.Methods: Genotypic profiling of CXCL8c.105A&gt;G and CXCL8c.210C&gt;T SNP polymorphism were carried out by polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) methods using HpyCH4VI and RsaI restriction enzymes. Polymorphism study was conducted on 151 randomly selected Polish HF bulls.Results: The genotype frequencies of CXCL8c.105A&gt;G SNPs polymorphism in the investigated Polish HF bulls were observed as 0.24%, 0.5% and 0.26% respectively, whereas, the genotype frequencies of CXCL8c.210C&gt;T SNPs polymorphism were observed as 0.27%, 0.5% and 0.23% respectively. Overall, the allele frequencies were recorded higher for “G’ allele for CXCL8c.105A&gt;G and “C” allele and CXCL8c.210C&gt;T SNP polymorphism. In both investigated SNP polymorphism, the state of genetic equilibrium was maintained in Polish HF bulls. Overall, the obtained results identified four haplotypes with the highest frequencies of CG (0.493%) and TA (0.476%) haplotypes, and the lowest frequencies of CA (0.02%) and TG (0.01%) haplotypes, respectively.Conclusions: Study concludes that both polymorphism could be further investigated for the trait-associated studies in the breeding population of Polish HF cattle.

Associations of IL-1β and IL-6 gene polymorphisms with Parkinson's disease.

The aim of this study was to explore the associations of interleukin-1β (IL-1β) and IL-6 gene polymorphisms with the pathogenesis of Parkinson's disease. A total of 200 patients with Parkinson's disease in our hospital were collected as the disease group. Meanwhile, 200 healthy subjects were taken as the control group. Peripheral blood samples were drawn from all research subjects. The polymorphic regions of IL-1β and IL-6 were amplified via polymerase chain reaction (PCR). Moreover, the polymorphisms were detected and analyzed, followed by further analysis based on the changes in gene expressions and Hoehn-Yahr grade of patients. The allele distributions at IL-1β rs571556428 (p=0.015) and IL-6 rs543214973 (p=0.012) were statistically different between control group and disease group. In disease group, the G allele frequency at IL-1β rs571556428 and T allele frequency at IL-6 rs543214973 were significantly higher (p<0.05). Genotype distributions at IL-1β rs572292175 (p=0.017) and rs571556428 (p=0.000), and IL-6 rs543214973 (p=0.002) in disease group were also different from those in control group. In addition, the frequencies of CT genotype at IL-1β rs572292175, AA genotype at IL-1β rs571556428 and AA genotype at IL-6 rs543214973 in disease group were significantly lower (p<0.05). After modeling and analysis, it was found that the distribution of recessive model at IL-1β rs571556428 (p=0.012) and IL-6 rs543214973 (p=0.014) in disease group exhibited significant differences from those in control group. The frequencies of TA haplotype at IL-1β rs572292175 and rs571556428 (p=0.038) and GA haplotype at IL-6 rs1474348 and rs543214973 (p=0.047) in disease group were lower than those in control group (p<0.05). The polymorphisms at IL-1β rs571556428 and IL-6 rs1474348 were significantly associated with gene expression (p<0.05). Moreover, the expressions of IL-1β and IL-6 rose significantly in patients with GG genotype at rs571556428 and CG genotype at rs1474348, respectively (p<0.05). Furthermore, the polymorphism at IL-1β rs571556428 was significantly correlated with the grade of Parkinson's disease (p=0.000). Parkinson's disease was in a higher grade (grade 4-5) in patients with AA genotype, whereas in a lower grade (grade 1-2) in patients with GG and AG genotypes. IL-1β and IL-6 gene polymorphisms are significantly associated with the pathogenesis of Parkinson's disease.

Investigation of the Association between 45 Tag SNPs and Type 2 Diabetes Mellitus in Han Chinese Adults: A Prospective Cohort Study

Introduction: The objective of this study was to examine the association between type 2 diabetes mellitus (T2DM) and genes identified in previous genome-wide association studies (GWASs) in rural Han Chinese adults. Methods: This prospective study included 1,832 adults aged ≥18 years in Deqing without diabetes at baseline. The subjects were followed up for 8.7 years on average. We selected 45 susceptible tag single-nucleotide polymorphisms (SNPs) for T2DM that have been identified in GWASs and genotyped. A Cox model was constructed to calculate the adjusted hazard ratios (aHRs) for the association between SNPs and incident T2DM. Results: The incidence rate of T2DM was 12.0 per 1,000 person-years. After adjustment for covariates and a Bonferroni correction, rs17584499 of protein tyrosine phosphatase, receptor-type D (PTPRD), rs11257655 and rs10906115 of cell division cycle 123 gene (CDC123), and rs12970134 of melanocortin-4 receptor (MC4R) were significantly associated with incident T2DM. The aHRs for incident T2DM were 1.75 (95% confidence interval [CI]: 1.28–2.40) and 1.61 (95% CI: 1.27–2.04) in association with an increasing number of T alleles in rs17584499 and rs11257655 under an additive genetic model, and the aHR was 1.72 (95% CI: 1.33–2.22) with an increasing number of A alleles in rs10906115. The aHRs under the dominant model were 1.82 (95% CI: 1.25–2.66) for TT + CT versus CC of rs17584499 and 2.04 (95% CI: 1.47–2.86) for AA + AG versus GG of rs10966115. The aHRs under the recessive model were 2.99 (95% CI: 1.30–6.89) for TT versus CT + CC of rs17584499, 1.92 (95% CI: 1.39–2.70) for TT versus CT + CC of rs11257655, and 2.54 (95% CI:1.22–5.29) for AA versus AG + GG of rs12970134. In addition, an increased incidence of T2DM was significantly associated with the TA haplotype of rs11257655 and rs10906115 (aHR = 1.81, 95% CI: 1.12–2.92), while a decreased incidence was associated with the CG haplotype (aHR = 0.49, 95% CI: 0.35–0.68) and the CT haplotype of rs1111875 and rs5015480 (aHR = 0.61, 95% CI: 0.37–0.98). Conclusion: Variants of the PTPRD, CDC123, and MC4R genes were associated with the T2DM incidence in a rural Han Chinese population.

Association of HLA-DQ and IL13 gene variants with challenge-proven shrimp allergy in West Bengal, India.

Little is known about genetic factors and mechanisms underlying shrimp allergy. Genome-wide association studies identified HLA class-II and IL13 genes as highly plausible candidates for shrimp allergy. The present study was designed to investigate potential associations of HLA-DQ rs9275596, IL13 rs20541, and IL13 rs1800925 polymorphisms with challenge-proven shrimp allergy using the data from 532 people of West Bengal, India; selected on basis of positive skin prick test, elevated specific IgE and medical history. Risk genotypes, i.e., HLA-DQ rs9275596 CC, IL13 rs20541 AA, and IL13 rs1800925 TT, were found to be significantly associated with challenge positive shrimp allergy (P=0.04, 0.01, and 0.03, respectively). Distribution of genotypes for HLA-DQ and IL13 polymorphisms in allergic and control subjects showed significant difference between younger (20-40years) and older (>40years) age group (P=0.006). Risk genotypes significantly associated with elevated shrimp-specific IgE. IL13 TA haplotype significantly associated with shrimp allergy and elevated specific IgE (P=0.02). Synergistic effect of IL13 TA haplotype-HLA-DQ rs9275596 CC genotype interaction significantly elevated specific IgE (P=0.03). The present study suggests that HLA-DQ and IL13 polymorphisms pose major risk for shrimp allergic patients in West Bengal, India and thus could be helpful for early target-specific therapeutic intervention in near future.

Genetic variants of ZNF385B and COMT are associated with autism spectrum disorder in the Bangladeshi children

BackgroundAutism spectrum disorder (ASD) is an intense, highly heritable complex neurodevelopmental disorder in children. Genetic association studies have demonstrated the correlation of different genetic polymorphisms with ASD. We investigated the contribution of genetic variants in ZNF385B (rs11885327 and rs1964081) and COMT (rs165774) genes with Bangladeshi ASD children in this study. Material and methodsA total of 216 ASD cases and 216 controls were recruited in this case-control study, and the association of rs11885327, rs1964081, and rs165774 were examined by PCR–RFLP method. ResultsFor rs11885327, CC genotype, dominant model, and ‘C’ allele were significantly associated with ASD (OR = 1.89, 95% CI = 1.11–3.23, p = 0.019; OR = 1.51, 95% CI = 1.01–2.25, p = 0.043; OR = 1.40, 95% CI = 1.07–1.84, p = 0.013, respectively). After Bonferroni correction (p < 0.017), only ‘C’ allele remained significant. In the case of rs1964081, GG genotype (OR = 1.95, 95% CI = 1.07–3.57, p = 0.029) and ‘G’ allele (OR = 1.34, 95% CI = 1.02–1.76, p = 0.037) showed a significantly elevated risk for the development of ASD but the significance did not exist after Bonferroni correction. For rs165774, all genetic models were associated with an increased risk of ASD except AG genotype (AA vs. GG: OR = 7.68, 95% CI = 3.89–15.15, p < 0.0001; dominant model: OR = 2.29, 95% CI = 1.55–3.36, p < 0.0001; recessive model: OR = 6.54, 95% CI = 3.40–12.57, p < 0.0001; A allele: OR = 2.53, 95% CI = 1.88–3.39, p < 0.0001). In all cases, the results were statistically significant and the significance remained after Bonferroni correction (p < 0.017). Haplotyping analysis of rs11885327 and rs1964081 revealed that TA haplotype reduced the risk risk of ASD. ConclusionThe findings of this study indicate that rs11885327 and rs1964081 of ZNF385B and rs165774 of COMT genes contribute to the susceptibility of ASD in the Bangladeshi children.

An Exploratory Association Analysis of ABCB1 rs1045642 and ABCB1 rs4148738 with Non-Major Bleeding Risk in Atrial Fibrillation Patients Treated with Dabigatran or Apixaban.

(1) Background: The approach of bleeding complications in patients treated with non-vitamin K oral anticoagulants (NOACs) represents an important issue in clinical practice. Both dabigatran and apixaban are substrates for P-glycoprotein and, therefore, ABCB1 gene variations may be useful in individualizing NOACs treatment, especially in high-risk patients. (2) Methods: ABCB1 rs1045642 and rs4148738 were determined in 218 atrial fibrillation patients treated with dabigatran or apixaban (70.94 ± 9.04 years; 51.83% men). (3) Results: Non-major bleeding appeared in 7.34% NOACs–treated patients. The logistic tested models based on the four genetic models revealed no significant association between the variant genotype of two ABCB1 SNPs and the risk of bleeding (p > 0.05). Among the four two-locus haplotypes, TA and CA haplotypes had the highest frequency in NOACs-treated patients with bleeding, involving a possible positive association with the susceptibility of bleeding complications (OR = 1.04 and OR = 1.91, respectively). The logistic model found no significant association of estimated haplotypes with bleeding (p > 0.05) except for the TG haplotype which had a trend toward statistical significance (p = 0.092). Among the risk factors for bleeding, only age > 70 years and stroke/TIA showed a tendency toward statistical significance. (4) Conclusions: We found no significant associations between the studied ABCB1 variant genotypes with non-major bleeding risk in NOACs-treated patients. A trend of association between TG haplotype with bleeding risk was observed, implying a protective role of this haplotype against bleeding in patients treated with dabigatran or apixaban.