scholarly journals Common genetic variants and pathways in diabetes and associated complications and vulnerability of populations with different ethnic origins

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sabrina Samad Shoily ◽  
Tamim Ahsan ◽  
Kaniz Fatema ◽  
Abu Ashfaqur Sajib
Keyword(s):  
Diabetes Mellitus ◽  
Chronic Kidney Disease ◽  
Genetic Variants ◽  
Nucleotide Polymorphisms ◽  
Differential Distribution ◽  
East Asians ◽  
Single Nucleotide ◽  
Common Genetic Variants ◽  
Haplotype Frequencies ◽  
Variant Alleles

AbstractDiabetes mellitus is a complex and heterogeneous metabolic disorder which is often pre- or post-existent with complications such as cardiovascular disease, hypertension, inflammation, chronic kidney disease, diabetic retino- and nephropathies. However, the frequencies of these co-morbidities vary among individuals and across populations. It is, therefore, not unlikely that certain genetic variants might commonly contribute to these conditions. Here, we identified four single nucleotide polymorphisms (rs5186, rs1800795, rs1799983 and rs1800629 in AGTR1, IL6, NOS3 and TNFA genes, respectively) to be commonly associated with each of these conditions. We explored their possible interplay in diabetes and associated complications. The variant allele and haplotype frequencies at these polymorphic loci vary among different super-populations (African, European, admixed Americans, South and East Asians). The variant alleles are particularly highly prevalent in different European and admixed American populations. Differential distribution of these variants in different ethnic groups suggests that certain drugs might be more effective in selective populations rather than all. Therefore, population specific genetic architectures should be considered before considering a drug for these conditions.

scholarly journals Plasma interleukin-21 levels and genetic variants are associated with susceptibility to rheumatoid arthritis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Youguo Hao ◽  
Lijun Xie ◽  
Jing Xia ◽  
Zhen Liu ◽  
Baoxiu Yang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Genetic Variants ◽  
Chinese Population ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Das28 Score ◽  
Single Nucleotide ◽  
Chronic Inflammatory Condition ◽  
Chinese Subjects ◽  
Pro Inflammatory Cytokines

Abstract Background Rheumatoid Arthritis (RA) is a chronic inflammatory condition characterized by autoantibodies development and an elevated spectrum of pro-inflammatory cytokines. Previous reports highlighted a relationship between IL-21and the pathogenesis of RA. Although elevated IL-21 levels have been reported in RA patients, the association of common IL-21 genetic variants with a predisposition to RA development in the Chinese population lacks. Materials and methods Five hundred and fourteen Chinese subjects (healthy controls: 303 and rheumatoid arthritis patients: 211) were enrolled in the study. Clinical data of patients were collected from medical records, and patients were treated as per the guidelines. Common single nucleotide polymorphisms in the IL-21 gene (rs907715, rs2221903, rs2055979 and rs6822844) were genotyped by TaqMan SNPs genotyping method. IL-21 level in plasma of RA patients and healthy subjects was measured by ELISA. Results The plasma level of IL-21 was significantly higher in subjects with rheumatoid arthritis relative to healthy controls (p < 0.0001). A positive correlation was observed between IL-21 level and DAS28 score, indicating the association of the cytokine with the worsening of the disease (Spearman r = 0.61, p < 0.0001). The prevalence of AA genotype (rs2055979) was significantly higher in RA subjects than in the controls (p < 0.0001, χ2 = 34.73, OR = 4.34, 95% CI = 2.623 to 7.219). Furthermore, elevated plasma IL-21 was observed in the rs2055979-AA genotype compared to CC type (p < 0.0001). Conclusion IL-21 plays a crucial function in rheumatoid arthritis pathogenesis. IL-21 rs2055979 polymorphism is associated with IL-21 plasma levels and is predisposed to RA development in the Chinese population.

scholarly journals Genetic Polymorphisms of Pharmacogenes among the Genetically Isolated Circassian Subpopulation from Jordan

2020 ◽  
Vol 10 (1) ◽  
pp. 2 ◽  
Author(s):  
Laith N. AL-Eitan ◽  
Doaa M. Rababa’h ◽  
Nancy M. Hakooz ◽  
Mansour A. Alghamdi ◽  
Rana B. Dajani
Keyword(s):  
Genetic Variants ◽  
Rare Variants ◽  
Optimal Dose ◽  
Nucleotide Polymorphisms ◽  
Treatment Efficiency ◽  
Isolated Populations ◽  
Single Nucleotide ◽  
Interindividual Variations ◽  
Different Populations ◽  
Pharmacogenomic Studies

Several genetic variants have been identified that cause variation among different populations and even within individuals of a similar descent. This leads to interindividual variations in the optimal dose of the drug that is required to sustain the treatment efficiency. In this study, 56 single nucleotide polymorphisms (SNPs) within several pharmacogenes were analyzed in 128 unrelated subjects from a genetically isolated group of Circassian people living in Jordan. We also compared these variant distributions to other ethnic groups that are available at two databases (Genome 1000 and eXAC). Our results revealed that the distribution of allele frequencies within genes among Circassians in Jordan showed similarities and disparities when compared to other populations. This study provides a powerful base for clinically relevant SNPs to enhance medical research and future pharmacogenomic studies. Rare variants detected in isolated populations can significantly guide to novel loci involved in the development of clinically relevant traits.

Susceptible genes of restless legs syndrome in migraine

Cephalalgia ◽  
2016 ◽  
Vol 36 (11) ◽  
pp. 1028-1037 ◽  
Author(s):  
Jong-Ling Fuh ◽  
Ming-Yi Chung ◽  
Shu-Chih Yao ◽  
Ping-Kun Chen ◽  
Yi-Chu Liao ◽  
...  
Keyword(s):  
Restless Legs Syndrome ◽  
Genetic Variants ◽  
Multivariate Regression ◽  
Iron Homeostasis ◽  
Nucleotide Polymorphisms ◽  
Regression Analyses ◽  
Single Nucleotide ◽  
Association Analyses ◽  
Restless Legs ◽  
Increased Risk

Objective Several genetic variants have been found to increase the risk of restless legs syndrome (RLS). The aim of the present study was to determine if these genetic variants were also associated with the comorbidity of RLS and migraine in patients. Methods Thirteen single-nucleotide polymorphisms (SNPs) at six RLS risk loci ( MEIS1, BTBD9, MAP2K5, PTPRD, TOX3, and an intergenic region on chromosome 2p14) were genotyped in 211 migraine patients with RLS and 781 migraine patients without RLS. Association analyses were performed for the overall cohort, as well as for the subgroups of patients who experienced migraines with and without aura and episodic migraines (EMs) vs. chronic migraines (CMs). In order to verify which genetic markers were potentially related to the incidence of RLS in migraine patients, multivariate regression analyses were also performed. Results Among the six tested loci, only MEIS1 was significantly associated with RLS. The most significant SNP of MEIS1, rs2300478, increased the risk of RLS by 1.42-fold in the overall cohort ( p = 0.0047). In the subgroup analyses, MEIS1 augmented the risk of RLS only in the patients who experienced EMs (odds ratio (OR) = 1.99, p = 0.0004) and not those experiencing CMs. Multivariate regression analyses further showed that rs2300478 in MEIS1 (OR = 1.39, p = 0.018), a CM diagnosis (OR = 1.52, p = 0.022), and depression (OR = 1.86, p = 0.005) were independent predictors of RLS in migraine. Conclusions MEIS1 variants were associated with an increased risk of RLS in migraine patients. It is possible that an imbalance in iron homeostasis and the dopaminergic system may represent a link between RLS incidence and migraines.

Abstract 2924: Association of NOS1AP Genetic Variants with QT Interval Duration in Families from the Diabetes Heart Study

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Allison B Lehtinen ◽  
Christopher Newton-Cheh ◽  
Julie T Ziegler ◽  
Carl D Langefeld ◽  
Barry I Freedman ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Qt Interval ◽  
Genetic Model ◽  
Additive Model ◽  
Adaptor Protein ◽  
European Ancestry ◽  
Nucleotide Polymorphisms ◽  
Interval Duration ◽  
Common Genetic Variants ◽  
Qt Interval Duration

Background: Prolongation of the electrocardiographic QT interval is a risk factor for sudden cardiac death (SCD) in unselected samples as well as in post-myocardial infarction patients or those with diabetes. Common genetic variants in the nitric oxide synthase 1 adaptor protein (NOS1AP) gene have been reported to be associated with QT interval duration in individuals of European ancestry. We sought to replicate the association of NOS1AP variants with QT interval duration in pedigrees enriched for type 2 diabetes mellitus (T2DM). Methods and Results: Two single nucleotide polymorphisms (SNPs) in the NOS1AP gene, rs10494366 and rs10918594, were genotyped in a collection of 937 European Americans (EAs) and 177 African Americans (AAs) in 450 pedigrees containing at least two siblings with T2DM. An additive genetic model was tested for each SNP in ancestry-specific analyses using SOLAR in the total sample and in the diabetic subset (EA n=778, AA n=159), with and without exclusion of QT-altering medications. In the EA individuals, rs10494366 minor allele homozygotes had an 8.9 msec longer mean QT interval compared to major homozygotes (additive model p=4.4x10 -3 ); rs10918594 minor homozygotes had a 12.9 msec longer mean QT interval compared to major homozygotes (p=9.9x10 -5 ). Excluding users of QT-altering medications in the diabetic-only EA sample (n=514) strengthened the association despite the reduction in sample size (20.6 msec difference, p=2.0x10 -5 ; 23.4 msec difference, p=8.9x10 -7 , respectively). No association between the NOS1AP SNPs and QT interval duration was observed in the limited number of AA individuals examined. Conclusions: Two NOS1AP SNPs are strongly associated with QT interval duration in a predominately diabetic EA sample. Stronger effects of NOS1AP variants in diabetic individuals compared to previously reported unselected samples suggest that this patient subset may be particularly susceptible to genetic variants that influence myocardial depolarization and repolarization as manifest in the QT interval.

Causal associations of obesity with chronic kidney disease and arterial stiffness: a Mendelian randomization study

2021 ◽  
Author(s):  
Chaojie Ye ◽  
Lijie Kong ◽  
Zhiyun Zhao ◽  
Mian Li ◽  
Shuangyuan Wang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Standard Deviation ◽  
Kidney Disease ◽  
Single Nucleotide Polymorphisms ◽  
Arterial Stiffness ◽  
Genetic Risk ◽  
Mendelian Randomization ◽  
Genetic Risk Score ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

Abstract Purpose Observational studies have associated obesity with chronic kidney disease (CKD) and arterial stiffness, but the causality remains unclear. We aimed to investigate the causality of obesity with CKD and arterial stiffness using Mendelian randomization (MR) analysis. Methods We genotyped 14 body mass index (BMI)-associated variants validated in East Asians in 11384 Chinese adults. A genetic risk score based on the 14 variants and the 14 individual single nucleotide polymorphisms were respectively used as instrumental variables (IVs). CKD was defined as estimated glomerular filtration rate &lt;60 mL/min/1.73 m 2. Arterial stiffness was defined as brachial-ankle pulse wave velocity &gt;1550 cm/s. Results Using the genetic risk score as the IV, we demonstrated causal relations of each 1-standard deviation increment in BMI with CKD (odds ratio [OR]: 2.36; 95% confidence interval [CI]: 1.11-5.00) and arterial stiffness (OR: 1.71; 95% CI: 1.22-2.39). Using the 14 single nucleotide polymorphisms individually as IVs, each 1-standard deviation increment in BMI casually associated with CKD (OR: 2.58; 95% CI: 1.39-4.79) and arterial stiffness (OR: 1.87; 95% CI: 1.24-2.81) in the inverse-variance weighted analysis, and MR-Egger regression revealed no evidence of horizontal pleiotropy (Both P for intercept≥0.34). The causality between obesity and CKD was validated in two-sample MR analysis among Europeans (681275 of Genetic Investigation of ANthropometric Traits and 133413 of CKD Genetics). Conclusions This study provided novel insights into causality of obesity with CKD and arterial stiffness, highlighting the importance of weight management for primary prevention and control of subclinical vascular diseases.

scholarly journals Genetic Variants of DNA Repair Genes as Predictors of Radiation-Induced Subcutaneous Fibrosis in Oropharyngeal Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Ankita Gupta ◽  
Don Mathew ◽  
Shabir Ahmad Bhat ◽  
Sushmita Ghoshal ◽  
Arnab Pal
Keyword(s):  
Dna Repair ◽  
Genetic Variants ◽  
Oropharyngeal Carcinoma ◽  
Dna Repair Genes ◽  
Nucleotide Polymorphisms ◽  
Radical Radiotherapy ◽  
Single Nucleotide ◽  
Radiation Induced ◽  
Repair Genes ◽  
Severe Fibrosis

PurposeTo investigate the impact of genetic variants of DNA repair and pro-fibrotic pathway genes on the severity of radiation-induced subcutaneous fibrosis in patients of oropharyngeal carcinoma treated with radical radiotherapy.Materials and MethodsPatients of newly diagnosed squamous cell carcinoma of oropharynx being treated with two-dimensional radical radiotherapy were enrolled in the study. Patients who had undergone surgery or were receiving concurrent chemotherapy were excluded. Patients were followed up at 6 weeks post completion of radiotherapy and every 3 months thereafter for a median of 16 months. Subcutaneous fibrosis was graded according to the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) grading system and the maximum grade was recorded over the length of the patient’s follow-up. Patients with severe fibrosis (≥G3), were compared to patients with minor (≤G2) fibrotic reactions. Eight single nucleotide polymorphisms of 7 DNA repair genes and 2 polymorphisms of a single pro-fibrotic pathway gene were analyzed by Polymerase Chain Reaction and Restriction Fragment Length Polymorphism and were correlated with the severity of subcutaneous fibrosis.Results179 patients were included in the analysis. Subcutaneous fibrosis was seen in 168 (93.9%) patients. 36 (20.1%) patients had severe (grade 3) fibrosis. On multivariate logistic regression analysis, Homozygous CC genotype of XRCC3 (722C&gt;T, rs861539) (p=0.013*, OR 2.350, 95% CI 1.089-5.382), Homozygous AA genotype of ERCC4 Ex8 (1244G&gt;A, rs1800067) (p=0.001**, OR 11.626, 95% CI 2.490-275.901) and Homozygous TT genotype of XRCC5 (1401G&gt;T, rs828907) (p=0.020*, OR 2.188, 95% CI 1.652-7.334) were found to be predictive of severe subcutaneous fibrosis. On haplotype analysis, the cumulative risk of developing severe fibrosis was observed in patients carrying both haplotypes of variant Homozygous AA genotype of ERCC4 Ex8 (1244G&gt;A, rs1800067) and Homozygous TT genotype of XRCC5 (1401 G&gt;T, rs828907) (p=0.010*, OR 26.340, 95% CI 4.014-76.568).ConclusionWe demonstrated significant associations between single nucleotide polymorphisms of DNA repair genes and radiation-induced subcutaneous fibrosis in patients of oropharyngeal carcinoma treated with radiotherapy. We propose to incorporate these genetic markers into predictive models for identifying patients genetically predisposed to the development of radiation-induced fibrosis, thus guiding personalized treatment protocols.

scholarly journals Genetic variants associated with beta-cell function and insulin sensitivity potentially influence bile acid metabolites and gestational diabetes mellitus in a Chinese population

2021 ◽  
Vol 9 (1) ◽  
pp. e002287
Author(s):  
Qiulun Zhou ◽  
Ying Wang ◽  
Yuqin Gu ◽  
Jing Li ◽  
Hui Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Beta Cell ◽  
Genetic Variants ◽  
Cell Function ◽  
Chinese Women ◽  
Risk Scores ◽  
Nucleotide Polymorphisms ◽  
Mediation Analyses

IntroductionTo investigate associations between genetic variants related to beta-cell (BC) dysfunction or insulin resistance (IR) in type 2 diabetes (T2D) and bile acids (BAs), as well as the risk of gestational diabetes mellitus (GDM).Research design and methodsWe organized a case-control study of 230 women with GDM and 217 without GDM nested in a large prospective cohort of 22 302 Chinese women in Tianjin, China. Two weighted genetic risk scores (GRSs), namely BC-GRS and IR-GRS, were established by combining 39 and 23 single nucleotide polymorphisms known to be associated with BC dysfunction and IR, respectively. Regression and mediation analyses were performed to evaluate the relationship of GRSs with BAs and GDM.ResultsWe found that the BC-GRS was inversely associated with taurodeoxycholic acid (TDCA) after adjustment for confounders (Beta (SE)=−0.177 (0.048); p=2.66×10−4). The BC-GRS was also associated with the risk of GDM (OR (95% CI): 1.40 (1.10 to 1.77); p=0.005), but not mediated by TDCA. Compared with individuals in the low tertile of BC-GRS, the OR for GDM was 2.25 (95% CI 1.26 to 4.01) in the high tertile. An interaction effect of IR-GRS with taurochenodeoxycholic acid (TCDCA) on the risk of GDM was evidenced (p=0.005). Women with high IR-GRS and low concentration of TCDCA had a markedly higher OR of 14.39 (95% CI 1.59 to 130.16; p=0.018), compared with those with low IR-GRS and high TCDCA.ConclusionsGenetic variants related to BC dysfunction and IR in T2D potentially influence BAs at early pregnancy and the development of GDM. The identification of both modifiable and non-modifiable risk factors may facilitate the identification of high-risk individuals to prevent GDM.

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