| RE Type | NER1 | NER2 | Sentence | Paper Id |
|---|---|---|---|---|
| gene-disease | HIF | HAPE | The subjects carrying the AA ancestral genotype of EGLN1 rs2153364 (A/G)and the GA heterozygous genotype of EPAS1 rs13419896 (G/A) were at high risk for HAPE.The present studyprovides somesuggestive information about the EPAS1 and EGLN1 genes in association with HAPE susceptibility in regards to the HIF signaling pathway. | 356 |
| gene-disease | PHD2 | hypoxia | EPAS1 encodes the hypoxia-inducible-factor-2alpha (HIF2A)protein,which shares 48% sequence identitywith HIF1A(cid:50892)(cid:50893)(cid:50903).Similar to HIF1A,EPAS1 is stimulated by hypoxic conditions and heterodimer-izes with HIF2B for transcriptional activation of target genes(cid:50896)(cid:50903)In contrast, EGLN1 encodes prolylprolyl hydroxylase domain protein 2(PHD2),which senses hypoxia and negatively affects the activity of HIF2A and plays a regulatory role in mammalian oxygen homeostasis(cid:50892)(cid:50895)(cid:50903) In.normoxia, HIF2Asubunits are marked for the ubiquitin-proteasome degradation pathway through hydroxylation of proline by PHD2. | 356 |
| gene-disease | EGLN1 | HAPE | Thus, the present gene-gene interaction analysis needs to be replicated in other populations with HAPE and proven by other technical analyses of gene-gene In conclusion, the present study demonstrated apotential association of the EPAS1×EGLN1 inter-action with HAPE susceptibility in the Japanese population, despite no associations detected in the single gene model. | 356 |
| gene-disease | EGLN1 | high altitude sickness | Clin Sci (Lond)124:479-489, 201315) Buroker NE, Ning XH, Zhou ZN, Li K, Cen WJ, Wu XF, Zhu WZ, Scott CR, Chen SH : EPAS1 and EGLN1 associations with high altitude sickness in Han and Tibetan Chinese at the Qinghai-Tibetan Plateau. | 356 |
| gene-disease | EPAS1 gene | HAPC | We enrolled 63 Tibetan HAPC patients and 131 matched healthy Tibetans as a control group, from the Yushu area in Qinghai where the altitude is greater than 3500 m. Eight single- nucleotide polymorphisms (SNPs) of the EPAS1 gene, including rs12619696, rs13420857, rs2881504, rs4953388, rs13419896, rs4953354, rs10187368, and rs7587138, were genotyped by the Sequenom MassARRAY SNP assay. | 357 |
| gene-disease | rs12619696 SNP | HAPC | Furthermore, the genotype GG rs13419896 differed significantly between HAPC and control groups with an OR of 0.062 (95% CI, 0.007 to 0.530; P ¼ .001; Furthermore, we found thatthere were significant differences in the allele frequency of the rs12619696rs12619696 SNP between the 2 groups (P ¼ .014; Table 2); the A allele was much more prevalent among the HAPC group (24.6%) than the control group (14.3%), with an OR of 0.513 (95% CI, 0.299 to 0.881). | 357 |
| gene-disease | EPAS1 gene | HAPC | In addition, the rs4953354 SNP was significantly associated with HAPC risk both under the dominant (OR, 0.399; 95% CI, 0.215 to 0.742; P ¼ .003) and recessive models of inheritance (OR, 3.674; 95% CI, 1.149 to 11.745; P ¼ .020; Table 2).DiscussionIn a previous study we genotyped 207 SNPs of the EPAS1 gene in Chr2: 46304028–46851921 in a sample of 31 healthy Tibetans. | 357 |
| gene-disease | EPAS1 gene | HAPC | The results suggested that the polymorphism in the EPAS1 gene is associated with adaptation to high altitude in Tibetans.15 Thus we hypothesized that Tibetans with HAPC may carry a different genotype and alleles, and we genotyped 8 SNPs of the EPAS1 gene, 7 of them located in the same region of Chr2: 46304028–46851921. | 357 |
| gene-disease | EPAS1 SNPs | HAPC | First, we did not measure other clinical parameters of the subjects, such as systolic blood pressure, diastolic blood pressure, mean arterial pressure, and pulmonary artery systolic pressure, which would provide more information on the significance of EPAS1 SNPs in Tibetans with HAPC. | 357 |
| gene-disease | EPAS1 SNPs | HAPC | More subjects will be included in the 2 groups to increase the power to detect the association of EPAS1 SNPs with HAPC in Tibetans. | 357 |
| gene-disease | hg18 | high altitude pulmonary edema | Yang YZ, Wang YP, Qi YJ, et al. Endothelial PAS domain protein 1 Chr2:46441523(hg18) polymorphism is associated with susceptibility to high altitude pulmonary edema in Han Chinese. | 357 |
| gene-disease | EPAS1 | HAPC | To explore the hereditary basis of high altitude polycythemia (HAPC) and investigate the association between EPAS1 and HAPC in the Han population, these 3 single nucleotide polymorphisms were assessed in 318 male Han Chinese HAPC patients and 316 control subjects. | 358 |
| gene-disease | HAPC | HAPC | Noncoding DNA sequences in or near EPAS1 are significantly different in the Tibetan and Han populations, and these regions are associated with low Hb concentration in Tibetans.23,24Three single nucleotide polymorphisms (SNPs) in non- coding regions—rs13419896, rs4953354, and rs1868092— not only show significant differences in frequencies between the Tibetan and Han populations,20 but alsoare associated with low Hb in Tibetans.24 To better understand the relationship between EPAS1 and HAPC in the Han population, we analyzed the genotypes and allele frequencies of the 3 SNPs, rs13419896 (A/G), rs4953354 (A/G), and rs1868092 (A/G), using the high resolution melting (HRM) method35,36 in male HAPC patients and control subjects from the Han population in the Qinghai-Tibetan plateau. | 358 |
| gene-disease | con- trol | HAPC | All 3 SNPs were in Hardy-Weinberg equilibrium in con- troltrol group rs13419896 (0.137), rs4953354 (0.170), and rs1868092 (0.227); and in HAPC patients rs13419896153rs13419896153 (48.4) 133 (42.1) 254 (80.4) 236 (74.7).34 (χ2 2.15, df 2).27 (χ2 2.65, df 2).64 (χ2 0.90, df 2)(0.963), rs4953354 (0.079), and rs1868092 (0.137). | 358 |
| gene-disease | EPAS1 | HAPC | Although significant differences in the alleles and genotypes frequencies of the 3 SNPs (rs13419896, rs4953354, and rs1868092) of EPAS1 were observed between the Tibetan and Han populations, our results showed no differences in the distribution of genotypes or alleles of the 3 SNPs between HAPC patients and control subjects from the Han population. | 358 |
| gene-disease | EPAS1 | HAPC | As a transcription factor, EPAS1 functions as targeting its downstream genes, such as iron absorption genes, which is essential for erythropoieses.41 It is also reported that mutation of EPAS1 exons would cause excessive erythrocytosis under normoxic conditions.42–45 Moreover, a polymor- phism in the intron of EPAS1chr2:46441523(hg18) was associated with chronic mountain sickness in Tibetans,46 and this polymorphism also showed great populations.23between TibetandifferencesHowever, even though DNA sequences of EPAS1 showed significant differences between Tibetan and Han populations, it is unclear whether expression or function of EPAS1 differs between these 2 groups, and the role of Hb in high altitude adaptation is still under discussion.47 This study leads us to reconsider the role that EPAS1 plays in HAPC in the Han population and in high altitude adaptation in the Tibetan population. | 358 |
| gene-disease | Hb | hypoxia | First, because the genotypes and alleles frequencies of the 3 SNPs showed no differences between HAPC and controls, it appears that the Hb concentration in the Han population at high altitude is not so greatly associated with SNPs as is reported in the Tibetan population.24 One possible explanation for this phenomenon is that Tibetans have experienced thousands of years of selective pressure by high altitude hypoxia.19–24,48 EPAS1 exhibits the strongest signatures of natural selection and might be expressed in the context of a unique genetic model in the Tibetan population in comparison with the Han population; this context could affect its downstream gene expression to result in the low Hb concentrations observed in Tibetans. | 358 |
| gene-disease | EPAS1 | HAPC | Although this study revealed no different distributions of the alleles or genotype frequencies of these 3 SNPs between HAPC patients and healthy controls, investigations should focus on finding more variants in or near EPAS1 and other genes that are associated with high altitude adaptation and erythropoiesis. | 358 |
| gene-disease | EPAS1 | HAPC | Moreover, we epigenetic modifications of EPAS1, such as DNA methylation and microRNA regulation, pathogenesis In conclusion, this study indicates that a variation of EPAS1 may be involved in the genetic susceptibility to HAPC in the Han population; and the G-G-G haplotype constructed by rs13419896, rs4953354, and rs1868092 in EPAS1 may increase the risk of HAPC in the male Han population. | 358 |
| gene-disease | JAK2 V617F mutation | poly- cythemia vera | Wu Z, Yuan H, Zhang X, et al. Development and inter- laboratory validation of unlabeled probe melting curve analysis for detection of JAK2 V617F mutation in poly- cythemia vera. | 358 |
| gene-disease | HIF2A gene | erythrocy- tosis | Percy MJ, Chung YJ, Harrison C, et al.mutations in the HIF2A gene associated with erythrocy- tosis. | 358 |
| gene-disease | HIF2A gene | Erythrocytosis | Van Wijk R, Sutherland S, Van Wesel AC, et al. Erythrocytosis associated with a novel missense mutation in the HIF2A gene. | 358 |
| gene-disease | EGLN1 | high altitude sickness | Buroker NE, Ning XH, Zhou ZN, et al. EPAS1 and EGLN1 associations with high altitude sickness in Han and Tibetan Chinese at the Qinghai-Tibetan Plateau. | 358 |
| gene-disease | hemoglobin | chronic mountain sickness | Tibetan highlanders are particularly resistant to developing chronic mountain sickness (4, 11), and exhibit little or no increase in hemoglobin concentration with increasing altitude, even at 4,000 m (13,200 ft) and only moderate increases beyond (12, 13). | 359 |
| gene-disease | HIF2α | hyp- oxia | The induction of erythrocytosis by hyp- oxia involves the hypoxia-inducible factor (HIF) family of tran- scription factors and, in particular, EPAS1 (or HIF2α) (24, 25).Three independent studies, but with mutually reinforcing results, were performed by groups that have since come together to form a consortium with the aim of reporting on the findings. | 359 |
| gene-disease | HIF2α | VHL | A larger number of cases have been reported for the slightly less specific genetic disorder of Chuvash Polycythemia, where ho- mozygosity for hypomorphic alleles for VHL results in elevatedlevels of both HIF1α and EPAS1/HIF2α (41). | 359 |
| gene-disease | EPAS1 | chronic mountain sickness | Although the similarity between chronic mountain sickness and the EPAS1 gain of function phenotype in lowlanders is striking, there nevertheless may be other aspects to the pheno- type that are not revealed at low altitude but are only revealed at high altitude, when oxygen availability is also limited. | 359 |
| gene-disease | EPAS1 | fetal growth restriction | In partic- ular, EPAS1 plays very important, if still poorly understood, roles in both placental and embryonic development (51–54) and pos- sibly also in the pathogenesis of fetal growth restriction (55). | 359 |
| gene-disease | HIF2 | pulmonary arterial hypertension | Gale DP, Harten SK, Reid CDL, Tuddenham EGD, Maxwell PH (2008) Autosomal dominant erythrocytosis and pulmonary arterial hypertension associated with an activating HIF2 α mutation. | 359 |
| gene-disease | HIF2AM535I mutation | familial erythrocytosis | Martini M, et al. (2008) A novel heterozygous HIF2AM535I mutation reinforces the role of oxygen sensing pathway disturbances in the pathogenesis of familial erythrocytosis. | 359 |