HP (Haptoglobin)是一種血液中的酸性糖蛋白，主要與游離血紅蛋白結(jié)合并防止游離血紅蛋白引起的氧化應(yīng)激。最新研究表明，HP在免疫調(diào)節(jié)、炎癥反應(yīng)和腫瘤生長等方面也起到了重要作用。HP的水平在某些腫瘤中顯著升高，與腫瘤的預(yù)后和治療效果有關(guān)。此外，一些研究還發(fā)現(xiàn)，HP可以通過調(diào)節(jié)腸道微生物群落的平衡來影響人體代謝和健康。

As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of heme iron and to prevent kidney damage. Haptoglobin also acts as an antioxidant, has antibacterial activity, and plays a role in modulating many aspects of the acute phase response. Hemoglobin/haptoglobin complexes are rapidly cleared by the macrophage CD163 scavenger receptor expressed on the surface of liver Kupfer cells through an endocytic lysosomal degradation pathway.; The uncleaved form of allele alpha-2 (2-2), known as zonulin, plays a role in intestinal permeability, allowing intercellular tight junction disassembly, and controlling the equilibrium between tolerance and immunity to non-self antigens.

1. findings suggest that rs5471 is a strong genetic determinant of HP levels in Ghanaians, and this seems to be characteristic of Africans PMID: 29772214
2. We report on the identification of a novel 72 kd Hb reactive species which is cross-linked to HDL and demonstrate that vitamin E in HDL is decreased in Hp 2-2 diabetes mellitus individuals. PMID: 29888289
3. zonulin appears not to be an inflammatory marker in CKD. It seems it also does not play a role in the disturbances of iron metabolism in CKD. Its physiological role remains to be elucidated. PMID: 29134616
4. High serum Haptoglobin levels, but not Hp1-Hp2 polymorphism is associated with polycystic ovary syndrome. PMID: 28900795
5. Hp 2-2 phenotype is an independent predictor of postoperative acute kidney injury and is associated with decreased short and long-term survival after cardiac surgery in patients with diabetes mellitus. PMID: 28982674
6. Due to its fluctuation, a single measurement of zonulin level is not recommended for assessment of intestinal barrier integrity. PMID: 28883692
7. Review/Meta-analysis: No association was found between the Hp gene variants and retinopathy in type 2 diabetics. PMID: 28758129
8. This study investigates the involvement of Hp glycosylation in gastric cancer. It examined the site-specific glycosylation of serum Hp, revealing the feasibility of glycoproteomic profiling as a powerful platform for potential diagnostic markers with high sensitivity and high specificity for gastric cancer. PMID: 29285644
9. Differentially expressed haptoglobin can serve as a potential biomarker for type 2 diabetic mellitus in the American Hispanic population. PMID: 28218436
10. identified that apolipoprotein-A1 and haptoglobin had significant predictive values for the prediction of recovery at 12 weeks in DILI, enabling the construction of a new prognostic panel, the DILI-ActiTest, which needs to be independently validated PMID: 29287080
11. HP genetic variation may have utility as a biomarker of insulin resistance and diabetes risk in Arab-Americans. PMID: 29039222
12. Given the importance of Hp glycosylation, its unknown and unclear biological complexity and significances, Hp glycosylation has become a major target in cancer research. Development of sensitive and specific detection of Hp glycosylation including large-scale validation may be significant steps forward to its clinical application. PMID: 26873173
13. Data suggest that serum haptoglobin may act as useful clinical serological biomarkers in progression and prognostic evaluation in non-small cell lung cancer (NSCLC). PMID: 27248178
14. Although better control may reduce the incidence of coronary artery disease in Type 1 diabetes, a residual risk related to the haptoglobin 2 allele remains. PMID: 27028131
15. Regardless of the haptoglobin genotype, haptoglobin is associated with prevention of endothelial cell apoptosis in diabetes. PMID: 28830235
16. study discovered a splice donor founder mutation in HP (NM_001126102.1:c.190 + 1G > C); this mutation occurs on the HP1 allele of the common copy number variant in HP and leads to loss of function of HP1; it associates with lower levels of haptoglobin, higher levels of non-high density lipoprotein cholesterol and greater risk of coronary artery disease PMID: 28398513
17. the minor allele (T) of rs8062041 appeared to be protective against African Trypanosomiasis; haptoglobin related protein (HPR) is adjacent to HP and is a component of the Trypanolytic factor; the HP and HPR locus is duplicated in some people; the rs8062041 variant may be associated with this duplication and it is possible that increased production of HPR is the cause of protection associated with rs806204 PMID: 29077717
18. These results suggest that the hippocampus of Hp 1-1 genetic carriers may be more vulnerable to the insults of poor glycemic control. PMID: 28860127
19. Our results show an association between increased early-pregnancy serum zonulin concentration and gestational diabetes, suggesting zonulin as a possible predictor for gestational diabetes. PMID: 28319108
20. Pilot study shows an association of the haptoglobin 2-2 genotype with low-grade inflammation, haptoglobin concentration and carotid artery intima-media thickness in multi-ethnic population from Singapore. PMID: 27190085
21. We conducted a replication study using a dataset outside of the Challenge, and found the association between TP53INP2 and ER-negative breast cancer was significant (p = 5.07x10-3). Expression of HP (16q22.2) showed a suggestive association with ER-negative breast cancer in the discovery phase (Z = 4.30, p = 1.70x10-5) although the association was not significant after Bonferroni adjustment. PMID: 28957356
22. Studies suggest an association of serum haptoglobin N-glycan variation with gastric cancer and might be a promising marker for the cancer screening. PMID: 28052004
23. These results were consistent with the data of the clinical specimens. miR-122a could be a positive factor of zonulin by targeting EGFR, which increased the intestinal epithelial permeability in vivo and in vitro. PMID: 28641303
24. Hp2 allele is associated with premature ischemic cardiovascular deaths after first-ever ischemic stroke. PMID: 28487337
25. Vitamin E may provide benefit in reducing cardiovascular disease in haptoglobin Hp2-2 genotype individuals with diabetes. PMID: 28451949
26. High serum levels of HP at baseline are associated with inadequate response of 12 weeks methotrexate treatment in recent-onset rheumatoid arthritis patients. PMID: 24863583
27. Celiac disease (CD) is associated with elevation of the circulating zonulin level, the value of which correlates with the density of enteroviruses in CD patients with severe atrophic changes in the small bowel mucosa, particularly in cases of concomitant type 1 diabetes. PMID: 27995404
28. Results show that zonulin was significantly higher in obese children when compared to healthy children, indicating a potential role of zonulin in the etiopathogenesis of obesity and related disturbances. PMID: 28008865
29. Our findings suggest that increased serum zonulin concentration, i.e., increased intestinal permeability, contributes to metabolic endotoxemia, systemic inflammation, and insulin resistance in overweight pregnant women PMID: 28285651
30. The present study demonstrated that the mRNA and protein expression levels of haptoglobin were increased in patients with psoriasis. PMID: 27571879
31. SCC-specific HP peptide HP216 may have a role in lung squamous cell carcinoma and could be a serum biomarker PMID: 26783151
32. Altered glycosylation, expression of serum haptoglobin and alpha-1-antitrypsin in chronic hepatitis C, hepatitis C induced liver cirrhosis and hepatocellular carcinoma patients. PMID: 27034286
33. In addition to predicting the incidence of cardio-renal complications, HP 2-2 also increases susceptibility for cardio-renal mortality in type 1 diabetes. PMID: 26684170
34. Findings suggest that the antioxidative and anti-inflammatory capacity of the Hp 2 is inferior to that of the Hp 1 allele. PMID: 26114833
35. The ratio of the fucosylated peaks to their corresponding nonfucosylated forms shows that the fucosylated glycans from haptoglobin are upregulated in the case of hepatocellular carcinoma samples versus cirrhosis samples. PMID: 26503433
36. The bifucosylated tetra-anntenary glycan of haptoglobin was upregulated in hepatocellular carcinoma patients of all etiologies. PMID: 26448449
37. Ovarian cancer cells express both Hp and its receptor CCR2 but only after exposure to ascitic fluid, inducing moderated cell migration; results suggest that Hp-induced changes in the cell morphology, actin cytoskeleton structure, and migration ability of tumor cells, is possibly "preparing" these cells for the potential induction of the metastatic phenotype. PMID: 26211665
38. Haptoglobin phenotype is unlikely to be an important modifier of cystic fibrosis phenotype. PMID: 26370551
39. Recurring exonic deletions in HP likely enhance human health by lowering cholesterol levels in the blood. PMID: 26901066
40. these results demonstrate that sHP is associated with poor prognosis of colorectal cancer patients and that HP promotes colorectal cancer cell invasion. PMID: 26756179
41. Haptoglobin 2-2 genotype was an independent predictor of cerebral salt wasting syndrome after subarachnoid hemorrhage. PMID: 26348010
42. Endothelial dysfunction may be influenced by Hp2/2 genotype in patients with type 1 diabetes with independence of classical CV risk factors. PMID: 26122942
43. This study suggests a possible role of haptoglobin phenotype on iron metabolism abnormalities that are observed in Parkinson disease. PMID: 26228081
44. The present study described differentially expressed human haptoglobin as a lung cancer serum protein biomarker, which may serve as a diagnostic and therapeutic target. PMID: 26005016
45. Hp 2 type is associated with elevated systolic pulmonary arterial pressure and low plasma nitrite levels in hemodialysis patients specifically in the diabetes mellitus state. PMID: 26171400
46. Serum levels of haptoglobin are higher in pancreatic cancer patients. PMID: 25861849
47. Patients with type 2 diabetes and poor glycaemic control carrying the Hp 1-1 genotype may be at increased risk of cognitive impairment, particularly in the attention/working memory domain. PMID: 25628235
48. Structure of the human Hp-Hb and Trypanosoma brucei brucei HpHbR protein complex is described. PMID: 25410714
49. Report increased numbers of highly fucosylated Haptoglobin alpha isoforms in ascitic fluids and the presence of fucosylated Haptoglobin in tumor tissues of ovarian cancer Mexican patients associated with advanced stages of the disease. PMID: 24576319
50. Serum zonulin levels are significantly elevated in newly diagnosed Chinese Type 2 diabetes patients, indicating a potential role of zonulin in the pathophysiology of type 2 diabetes in Chinese. PMID: 25238913

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Anhaptoglobinemia (AHP)

Secreted.

Peptidase S1 family

Expressed by the liver and secreted in plasma.

HGNC: 5141

OMIM: 140100

KEGG: hsa:3240

STRING: 9606.ENSP00000348170

UniGene: Hs.513711