scholarly journals Association between Genetic Variants and Diabetes Mellitus in Iranian Populations: A Systematic Review of Observational Studies

2015 ◽  
Vol 2015 ◽  
pp. 1-21 ◽  
Author(s):  
Mehrnoosh Khodaeian ◽  
Samaneh Enayati ◽  
Ozra Tabatabaei-Malazy ◽  
Mahsa M. Amoli
Keyword(s):  
Diabetes Mellitus ◽  
Systematic Review ◽  
Genetic Variants ◽  
Animal Studies ◽  
Association Studies ◽  
Foot Ulcer ◽  
Genome Wide Association Studies ◽  
Apo E ◽  
Iranian Populations

Introduction.Diabetes mellitus as the most prevalent metabolic disease is a multifactorial disease which is influenced by environmental and genetic factors. In this systematic review, we assessed the association between genetic variants and diabetes/its complications in studies with Iranian populations.Methods.Google Scholar, PubMed, Scopus, and Persian web databases were systematically searched up to January 2014. The search terms were “gene,” “polymorphism,” “diabetes,” and “diabetic complications”; nephropathy, retinopathy, neuropathy, foot ulcer, and CAD (coronary artery diseases); and Persian equivalents. Animal studies, letters to editor, and in vitro studies were excluded.Results.Out of overall 3029 eligible articles, 88 articles were included. We found significant association between CTLA-4, IL-18, VDR, TAP2, IL-12, and CD4 genes and T1DM, HNFαand MODY, haptoglobin, paraoxonase, leptin, TCF7L2, calreticulin, ERα, PPAR-γ2, CXCL5, calpain-10, IRS-1 and 2, GSTM1, KCNJ11, eNOS, VDR, INSR, ACE, apoA-I, apo E, adiponectin, PTPN1, CETP, AT1R, resistin, MMP-3, BChE K, AT2R, SUMO4, IL-10, VEGF, MTHFR, and GSTM1 with T2DM or its complications.Discussion.We found some controversial results due to heterogeneity in ethnicity and genetic background. We thought genome wide association studies on large number of samples will be helpful in identifying diabetes susceptible genes as an alternative to studying individual candidate genes in Iranian populations.

Genetic variants and magnetic resonance imaging measures in multiple sclerosis: a systematic review

10.20883/182 ◽  
2016 ◽  
Vol 85 (4) ◽  
pp. 311
Author(s):  
Jan Krzysztof Nowak ◽  
Izabela Guzikowska-Ruszkowska ◽  
Jadwiga Łopaciuch ◽  
Wiesława Jankowska ◽  
Ewa Piotrowska ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Systematic Review ◽  
Magnetic Resonance ◽  
Mr Imaging ◽  
Genetic Variants ◽  
Brain Atrophy ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Lesion Load ◽  
The Relationship

Introduction. Although environmental factors play the major role in the etiopathogenesis of multiple sclerosis (MS), genetic factors are implicated as well. We aimed to summarize the current knowledge on the relationship between genetic variants and magnetic resonance (MR) imaging measures in MS.Material and Methods. A systematic review. In December 2016, Scopus (since the year 1980; including MEDLINE) was searched for studies meeting predefined criteria designed to identify articles regarding: multiple sclerosis, genetic variants, and MR imaging. These were then analyzed to identify publications linking polymorphisms and MR findings.Results. The search yielded 290 items; 26 were included in the final analysis. Two genome‑wide association studies (GWAS) and two projects employing panels of a few dozen of genes of interest provided most of the data. The other publications concerned no more than 5 genes at a time. Twenty studies reported positive findings. The relationship between HLA‑DRB1*15:01 or BDNF rs6265 (Val66Met) and the radiologic course of MS was not consistent across the studies. An intersection of the results of the two GWAS yielded: OPCML (rs11223055), PTPRD (rs1953594), and WWOX (rs11150140, rs1116525) (brain atrophy) as well as CDH13 (rs692612) and PLCB1 (rs6118257) (lesion load).Conclusions. Genetic variants were shown to correlate with MS‑related brain atrophy and lesion load. Further research in the field is required.

scholarly journals Complex polymorphisms in endocytosis genes suggest alpha-cyclodextrin as a treatment for breast cancer

2017 ◽  
Author(s):  
Knut M. Wittkowski ◽  
Christina Dadurian ◽  
Martin P. Seybold ◽  
Han Sang Kim ◽  
Ayuko Hoshino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Animal Studies ◽  
Association Studies ◽  
Treatment Options ◽  
Cell Cycle Control ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Genome Wide ◽  
Estrogen Receptor Positive

AbstractMost breast cancer deaths are caused by metastasis and treatment options beyond radiation and cytotoxic drugs, which have severe side effects, and hormonal treatments, which are or become ineffective for many patients, are urgently needed. This study reanalyzed existing data from three genome-wide association studies (GWAS) using a novel computational biostatistics approach (muGWAS), which had been validated in studies of 600–2000 subjects in epilepsy and autism. MuGWAS jointly analyzes several neighboring single nucleotide polymorphisms while incorporating knowledge about genetics of heritable diseases into the statistical method and about GWAS into the rules for determining adaptive genome-wide significance.Results from three independent GWAS of 1000–2000 subjects each, which were made available under the National Institute of Health’s “Up For A Challenge” (U4C) project, not only confirmed cell-cycle control and receptor/AKT signaling, but, for the first time in breast cancer GWAS, also consistently identified many genes involved in endo-/exocytosis (EEC), most of which had already been observed in functional and expression studies of breast cancer. In particular, the findings include genes that translocate (ATP8A1, ATP8B1, ANO4, ABCA1) and metabolize (AGPAT3, AGPAT4, DGKQ, LPPR1) phospholipids entering the phosphatidylinositol cycle, which controls EEC. These novel findings suggest scavenging phospholipids via alpha-cyclodextrins (αCD) as a novel intervention to control local spread of cancer, packaging of exosomes (which prepare distant microenvironment for organ-specific metastases), and endocytosis of β1 integrins (which are required for spread of metastatic phenotype and mesenchymal migration of tumor cells).Beta-cyclodextrins (βCD) have already been shown to be effective inin vitroand animal studies of breast cancer, but exhibits cholesterol-related ototoxicity. The smaller αCDs also scavenges phospholipids, but cannot fit cholesterol. Anin-vitrostudy presented here confirms hydroxypropyl (HP)-αCD to be twice as effective as HPβCD against migration of human cells of both receptor negative and estrogen-receptor positive breast cancer.If the previous successful animal studies with βCDs are replicated with the safer and more effective αCDs, clinical trials of adjuvant treatment with αCDs are warranted. Ultimately, all breast cancer are expected to benefit from treatment with HPαCD, but women with triplenegative breast cancer (TNBC) will benefit most, because they have fewer treatment options and their cancer advances more aggressively.

Genetic variants in m6A modification genes are associated with esophageal squamous-cell carcinoma in the Chinese population

2020 ◽  
Vol 41 (6) ◽  
pp. 761-768
Author(s):  
Nan Yang ◽  
Pingting Ying ◽  
Jianbo Tian ◽  
Xiaoyang Wang ◽  
Shufang Mei ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Genetic Variants ◽  
Association Studies ◽  
Valuable Insight ◽  
Genome Wide Association Studies ◽  
Cancer Occurrence

Abstract N 6-methyladenosine (m6A) is an abundant modification in RNAs that affects RNA metabolism, and it is reported to be closely related to cancer occurrence and metastasis. In this study, we focused on evaluating the associations between genetic variants in m6A modification genes and the risk of esophageal squamous-cell carcinoma (ESCC). By integrating data of our previous genome-wide association studies and the predictions of several annotation tools, we identified a single nucleotide polymorphism, rs2416282 in the promoter of YTHDC2, that was significantly associated with the susceptibility of ESCC (odds ratio = 0.84, 95% CI: 0.77–0.92, P = 2.81 × 10−4). Through further functional experiments in vitro, we demonstrated that rs2416282 regulated YTHDC2 expression. Knockdown of YTHDC2 substantially promoted the proliferation rate of ESCC cells by affecting several cancer-related signaling pathways. Our results suggested that rs2416282 contributed to ESCC risk by regulating YTHDC2 expression. This study provided us a valuable insight into the roles of genetic variants in m6A modification genes for ESCC susceptibility and may contribute to the prevention of this disease in the future.

scholarly journals The Link between Aggrecan and Familial Osteochondritis Dissecans

Surgeries ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. 128-138
Author(s):  
Samantha Ozere ◽  
Sami Chergui ◽  
Megan E. Cooke ◽  
Thierry Pauyo ◽  
Derek H. Rosenzweig
Keyword(s):  
Osteochondritis Dissecans ◽  
Animal Studies ◽  
Association Studies ◽  
Treatment Options ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Future Research ◽  
Genome Wide Association Studies ◽  
Focal Lesions

Osteochondritis dissecans (OCD) is a chronic disease of the articular cartilage characterized by focal lesions of subchondral bone and overlaying cartilage. Through the growing number of reports describing the high prevalence of OCD in some families, the subcategory termed familial OCD (FOCD) was established. With the development of genetic approaches such as genome-wide association studies and sequencing, aggrecan (ACAN) has been identified as one of the genes of interest associated with FOCD. Aggrecan is a crucial protein for the preservation and function of cartilage. However, due to FOCD being characterized relatively recently, there is a paucity of literature on the subject. The purpose of this review is to explore the relationship between ACAN mutations and familial OCD as well as to explore current treatment options and avenues for future research. In vitro and animal studies have shown the importance of ACAN in the preservation of cartilage. However, the only human ACAN mutation related to OCD ever identified is a V2303M mutation in the G3 domain. Multiple treatments have been superficially explored, and some options such as growth hormone (GH) and gonadotrophin-releasing hormone agonists (GnRHa) show potential. Thus, further research on FOCD in needed to identify other ACAN mutations and determine optimal treatment modalities for this patient population.

scholarly journals Genetic variants of calcium and vitamin D metabolism in kidney stone disease

2019 ◽  
Author(s):  
Sarah A. Howles ◽  
Akira Wiberg ◽  
Michelle Goldsworthy ◽  
Asha L. Bayliss ◽  
Emily Grout ◽  
...  
Keyword(s):  
Vitamin D ◽  
Genetic Variants ◽  
Kidney Stone ◽  
Association Studies ◽  
Stone Disease ◽  
Calcium Excretion ◽  
Genome Wide Association Studies ◽  
Vitamin D Metabolism ◽  
Kidney Stone Disease

Kidney stone disease (nephrolithiasis) is a major clinical and economic health burden1,2 with a heritability of ~45-60%3. To identify genetic variants associated with nephrolithiasis we performed genome-wide association studies (GWAS) and meta-analysis in British and Japanese populations, including 12,123 nephrolithiasis cases and 416,928 controls. Twenty loci associated with nephrolithiasis were identified, ten of which are novel. A novel CYP24A1 locus is predicted to affect vitamin D metabolism and five loci, DGKD, DGKH, WDR72, GPIC1, and BCR, are predicted to influence calcium-sensing receptor (CaSR) signaling. In a validation cohort of nephrolithiasis patients the CYP24A1-associated locus correlated with serum calcium concentration and number of kidney stone episodes, and the DGKD-associated locus correlated with urinary calcium excretion. Moreover, DGKD knockdown impaired CaSR-signal transduction in vitro, an effect that was rectifiable with the calcimimetic cinacalcet. Our findings indicate that genotyping may inform risk of incident kidney stone disease prior to vitamin D supplementation and facilitate precision-medicine approaches, by targeting CaSR-signaling or vitamin D activation pathways in patients with recurrent kidney stones.

P4470Identification of four genes as novel susceptibility loci for early-onset type 2 diabetes mellitus, metabolic syndrome, or hyperuricemia in Japanese

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y Yamase ◽  
H Horibe ◽  
K Kato ◽  
M Oguri ◽  
T Fujimaki ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Metabolic Syndrome ◽  
Genetic Variants ◽  
Early Onset ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Susceptibility Loci ◽  
Genome Wide

Abstract Background Given that early-onset type 2 diabetes mellitus (T2DM), metabolic syndrome, and hyperuricemia have been shown to have strong genetic components, statistical power of a genetic association study may be increased by focusing on early-onset subjects with these conditions. Although genome-wide association studies have identified various genes and loci significantly associated with T2DM, metabolic syndrome, and hyperuricemia, genetic variants that contribute to predisposition to these conditions in Japanese individuals remain to be identified definitively. Purpose The purpose of the study was to identify genetic variants that confer susceptibility to early-onset T2DM, metabolic syndrome, or hyperuricemia in Japanese. We have now performed exome-wide association studies (EWASs) for early-onset subjects with T2DM, metabolic syndrome, or hyperuricemia and corresponding controls. Methods A total of 8102 individuals aged ≤65 years was enrolled in the study. The EWAS for T2DM was performed with 7407 subjects (1696 cases, 5711 controls), that for metabolic syndrome with 4215 subjects (2296 cases, 1919 controls), and that for hyperuricemia with 7919 subjects (1365 cases, 6554 controls). Single nucleotide polymorphisms (SNPs) were genotyped with Illumina Human Exome-12 DNA Analysis BeadChip or Infinium Exome-24 BeadChip arrays. The relation of allele frequencies for 31,210, 31,521, or 31,142 SNPs that passed quality control to T2DM, metabolic syndrome, or hyperuricemia, respectively, was examined with Fisher's exact test. To compensate for multiple comparisons of genotypes with T2DM, metabolic syndrome, or hyperuricemia, we applied Bonferroni's correction for statistical significance of association. Results The EWAS of allele frequencies revealed that four, six, or nine SNPs were significantly associated with T2DM (P<1.60 × 10–6), metabolic syndrome (P<1.59 × 10–6), or hyperuricemia (P<1.61 × 10–6), respectively. Multivariable logistic regression analysis with adjustment for age and sex revealed that three, six, or nine SNPs were significantly related to T2DM (P<0.0031), metabolic syndrome (P<0.0021), or hyperuricemia (P<0.0014). After examination of the association of identified SNPs to T2DM-, metabolic syndrome-, or hyperuricemia-related traits, linkage disequilibrium of the SNPs, and results of previous genome-wide association studies, we have newly identified ZNF860 and OR4F6 as susceptibility loci for T2DM, OR52E4 and OR4F6 for metabolic syndrome, and HERPUD2 for hyperuricemia. Conclusion Given that OR4F6 was significantly associated with both T2DM and metabolic syndrome, we thus newly identified four genes (ZNF860, OR4F6, OR52E4, HERPUD2) that confer susceptibility to early-onset T2DM, metabolic syndrome, or hyperuricemia. Determination of genotypes for the SNPs in these genes may prove informative for assessment of the genetic risk for T2DM, metabolic syndrome, or hyperuricemia in Japanese.

scholarly journals Genetic variants and magnetic resonance imaging measures in multiple sclerosis: a systematic review

2016 ◽  
Vol 85 (4) ◽  
pp. 311-316
Author(s):  
Jan Krzysztof Nowak ◽  
Izabela Guzikowska-Ruszkowska ◽  
Jadwiga Łopaciuch ◽  
Wiesława Jankowska ◽  
Ewa Piotrowska ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Systematic Review ◽  
Magnetic Resonance ◽  
Mr Imaging ◽  
Genetic Variants ◽  
Brain Atrophy ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Lesion Load ◽  
The Relationship

Introduction. Although environmental factors play the major role in the etiopathogenesis of multiple sclerosis (MS), genetic factors are implicated as well. We aimed to summarize the current knowledge on the relationship between genetic variants and magnetic resonance (MR) imaging measures in MS.Material and Methods. A systematic review. In December 2016, Scopus (since the year 1980; including MEDLINE) was searched for studies meeting predefined criteria designed to identify articles regarding: multiple sclerosis, genetic variants, and MR imaging. These were then analyzed to identify publications linking polymorphisms and MR findings.Results. The search yielded 290 items; 26 were included in the final analysis. Two genome-wide association studies (GWAS) and two projects employing panels of a few dozen of genes of interest provided most of the data. The other publications concerned no more than 5 genes at a time. Twenty studies reported positive findings. The relationship between HLA-DRB1*15:01 or BDNF rs6265 (Val66Met) and the radiologic course of MS was not consistent across the studies. An intersection of the results of the two GWAS yielded: OPCML (rs11223055), PTPRD (rs1953594), and WWOX (rs11150140, rs1116525) (brain atrophy) as well as CDH13 (rs692612) and PLCB1 (rs6118257) (lesion load).Conclusions. Genetic variants were shown to correlate with MS-related brain atrophy and lesion load. Further research in the field is required.

scholarly journals Identification of novel genetic variants associated with short stature in a Baka Pygmies population

2020 ◽  
Vol 139 (11) ◽  
pp. 1471-1483 ◽  
Author(s):  
Matteo Zoccolillo ◽  
Claudia Moia ◽  
Sergio Comincini ◽  
Davide Cittaro ◽  
Dejan Lazarevic ◽  
...  
Keyword(s):  
Short Stature ◽  
Genetic Variants ◽  
Complex Traits ◽  
Adult Height ◽  
Association Studies ◽  
Luciferase Assay ◽  
Phenotypic Characterization ◽  
Genome Wide Association Studies ◽  
Reduced Height

Abstract Human growth is a complex trait determined by genetic factors in combination with external stimuli, including environment, nutrition and hormonal status. In the past, several genome-wide association studies (GWAS) have collectively identified hundreds of genetic variants having a putative effect on determining adult height in different worldwide populations. Theoretically, a valuable approach to better understand the mechanisms of complex traits as adult height is to study a population exhibiting extreme stature phenotypes, such as African Baka Pygmies. After phenotypic characterization, we sequenced the whole exomes of a cohort of Baka Pygmies and their non-Pygmies Bantu neighbors to highlight genetic variants associated with the reduced stature. Whole exome data analysis revealed 29 single nucleotide polymorphisms (SNPs) significantly associated with the reduced height in the Baka group. Among these variants, we focused on SNP rs7629425, located in the 5′-UTR of the Hyaluronidase-2 (HYAL2) gene. The frequency of the alternative allele was significantly increased compared to African and non-African populations. In vitro luciferase assay showed significant differences in transcription modulation by rs7629425 C/T alleles. In conclusion, our results suggested that the HYAL2 gene variants may play a role in the etiology of short stature in Baka Pygmies population.

Sign in / Sign up

Export Citation Format

Share Document