Association Between Three SNPs and Thromboangiitis Obliterans in Xinjiang Uyghur Population

Shi, Zhenfeng; Fang, Qingbo; Sai, Li-mu; Jiareke, Tang; Ge, Xiaohu

doi:10.1089/gtmb.2015.0264

Cited by 10 publications

(6 citation statements)

References 32 publications

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“…Rs7632505 has recently been reported to be associated with thromboangiitis obliterans (OR = 29.47, p < 1e-04), a chronic peripheral vascular occlusive disease in a Xinjiang Uyghur Population (Shi et al, 2016 ). The dynamic effect of rs7632505 on CHD may be explained by the inhibitory effect of SEMA5B on angiogenesis which is related to aging process (Lähteenvuo and Rosenzweig, 2012 ) and is purported to be involved in atherosclerosis and other CVDs (Khurana et al, 2005 ; Deveza et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

Pleiotropic Meta-Analyses of Longitudinal Studies Discover Novel Genetic Variants Associated with Age-Related Diseases

Kernogitski

Kulminskaya

et al. 2016

Front. Genet.

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Age-related diseases may result from shared biological mechanisms in intrinsic processes of aging. Genetic effects on age-related diseases are often modulated by environmental factors due to their little contribution to fitness or are mediated through certain endophenotypes. Identification of genetic variants with pleiotropic effects on both common complex diseases and endophenotypes may reveal potential conflicting evolutionary pressures and deliver new insights into shared genetic contribution to healthspan and lifespan. Here, we performed pleiotropic meta-analyses of genetic variants using five NIH-funded datasets by integrating univariate summary statistics for age-related diseases and endophenotypes. We investigated three groups of traits: (1) endophenotypes such as blood glucose, blood pressure, lipids, hematocrit, and body mass index, (2) time-to-event outcomes such as the age-at-onset of diabetes mellitus (DM), cancer, cardiovascular diseases (CVDs) and neurodegenerative diseases (NDs), and (3) both combined. In addition to replicating previous findings, we identify seven novel genome-wide significant loci (< 5e-08), out of which five are low-frequency variants. Specifically, from Group 2, we find rs7632505 on 3q21.1 in SEMA5B, rs460976 on 21q22.3 (1 kb from TMPRSS2) and rs12420422 on 11q24.1 predominantly associated with a variety of CVDs, rs4905014 in ITPK1 associated with stroke and heart failure, rs7081476 on 10p12.1 in ANKRD26 associated with multiple diseases including DM, CVDs, and NDs. From Group 3, we find rs8082812 on 18p11.22 and rs1869717 on 4q31.3 associated with both endophenotypes and CVDs. Our follow-up analyses show that rs7632505, rs4905014, and rs8082812 have age-dependent effects on coronary heart disease or stroke. Functional annotation suggests that most of these SNPs are within regulatory regions or DNase clusters and in linkage disequilibrium with expression quantitative trait loci, implying their potential regulatory influence on the expression of nearby genes. Our mediation analyses suggest that the effects of some SNPs are mediated by specific endophenotypes. In conclusion, these findings indicate that loci with pleiotropic effects on age-related disorders tend to be enriched in genes involved in underlying mechanisms potentially related to nervous, cardiovascular and immune system functions, stress resistance, inflammation, ion channels and hematopoiesis, supporting the hypothesis of shared pathological role of infection, and inflammation in chronic age-related diseases.

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Section: Discussionmentioning

confidence: 99%

Pleiotropic Meta-Analyses of Longitudinal Studies Discover Novel Genetic Variants Associated with Age-Related Diseases

Kernogitski

Kulminskaya

et al. 2016

Front. Genet.

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“…Although it is not specific for LEAD, a case-control GWAS of 177 patients with thromboangiitis obliterans (TAO) identified three SNPs (rs376511 in the IL17RC gene, rs7632505 in the SEMA5B gene, and rs10178082 in the RPA3 gene) that were significantly associated with TAO in the Uighur population [ 33 ]. TAO is a progressive, recurrent inflammation and thrombosis of the small and medium-sized arteries and veins of the hands and feet.…”

Section: Heritability Of Atherosclerotic Lower Extremity Peripheral A...mentioning

confidence: 99%

“…Although the pathophysiological mechanisms underlying the occurrence of TAO and LEAD are different, the results of this study could contribute to the elucidation of the genetic architecture of LEAD. The IL17RC gene located on chromosome 3q25.3 is involved in the regulation of the inflammatory response [ 34 ], and the SEMA5B gene [ 35 ] located on chromosome 3q21.1 regulates axon growth during the development of the nervous system [ 25 , 33 , 35 ].…”

Section: Heritability Of Atherosclerotic Lower Extremity Peripheral A...mentioning

confidence: 99%

The Genetic Architecture of the Etiology of Lower Extremity Peripheral Artery Disease: Current Knowledge and Future Challenges in the Era of Genomic Medicine

Butnariu

Gorduza

Florea

et al. 2022

IJMS

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Lower extremity artery disease (LEAD), caused by atherosclerotic obstruction of the arteries of the lower limb extremities, has exhibited an increase in mortality and morbidity worldwide. The phenotypic variability of LEAD is correlated with its complex, multifactorial etiology. In addition to traditional risk factors, it has been shown that the interaction between genetic factors (epistasis) or between genes and the environment potentially have an independent role in the development and progression of LEAD. In recent years, progress has been made in identifying genetic variants associated with LEAD, by Genome-Wide Association Studies (GWAS), Whole Exome Sequencing (WES) studies, and epigenetic profiling. The aim of this review is to present the current knowledge about the genetic factors involved in the etiopathogenic mechanisms of LEAD, as well as possible directions for future research. We analyzed data from the literature, starting with candidate gene-based association studies, and then continuing with extensive association studies, such as GWAS and WES. The results of these studies showed that the genetic architecture of LEAD is extremely heterogeneous. In the future, the identification of new genetic factors will allow for the development of targeted molecular therapies, and the use of polygenic risk scores (PRS) to identify individuals at an increased risk of LEAD will allow for early prophylactic measures and personalized therapy to improve their prognosis.

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“…These results suggest that both KD and GPA may share SNPs in SEMA6A as a genetic risk factor associated with the subsequent male predominance of incidence. In addition, an association between an SNP in SEMA5B with thromboangiitis obliterans (TAO) was reported in a Xinjiang Uyghur population of China 124 …”

Section: Semaphorins and Kawasaki Diseasementioning

confidence: 99%

“…In addition, an association between an SNP in SEMA5B with thromboangiitis obliterans (TAO) was reported in a Xinjiang Uyghur population of China. 124…”

Section: Semaphorins and Kawasaki Diseasementioning

confidence: 99%

The role of semaphorins in cardiovascular diseases: Potential therapeutic targets and novel biomarkers

Yin

Zhang

et al. 2022

The FASEB Journal

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Semaphorins (Semas), which belongs to the axonal guidance molecules, include 8 classes and could affect axon growth in the nervous system. Recently, semaphorins were found to regulate other pathophysiological processes, such as immune response, oncogenesis, tumor angiogenesis, and bone homeostasis, through binding with their plexin and neuropilin receptors. In this review, we summarized the detailed role of semaphorins and their receptors in the pathological progression of various cardiovascular diseases (CVDs), highlighting that semaphorins may be potential therapeutic targets and novel biomarkers for CVDs.

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Association Between Three SNPs and Thromboangiitis Obliterans in Xinjiang Uyghur Population

Cited by 10 publications

References 32 publications

Pleiotropic Meta-Analyses of Longitudinal Studies Discover Novel Genetic Variants Associated with Age-Related Diseases

Pleiotropic Meta-Analyses of Longitudinal Studies Discover Novel Genetic Variants Associated with Age-Related Diseases

The Genetic Architecture of the Etiology of Lower Extremity Peripheral Artery Disease: Current Knowledge and Future Challenges in the Era of Genomic Medicine

The role of semaphorins in cardiovascular diseases: Potential therapeutic targets and novel biomarkers

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