The genetics of Henoch–Schönlein purpura: a systematic review and meta-analysis

Abstract

Henoch-Schönlein purpura (HSP) is the most common form of systemic vasculitis of unknown etiology. This study aimed at reviewing published studies investigating the association of genetic polymorphisms with HSP and its severity. We systematically reviewed all published data on genetic risk factors for HSP by searching MEDLINE. We also performed a meta-analysis of association studies of HLA-DRB1-01, 07, and 11, angiotensin I-converting enzyme (ACE) insertion/deletion (I/D) polymorphism. We identified 45 studies investigating polymorphisms in 39 genes in association with HSP and/or its severity. Most of these genes are involved in immunological and/or inflammatory responses or vasomotor regulation. Most results were negative. The most convincing finding is the association of HLA-DRB1 01, 07, and 11 with HSP susceptibility. The overall odds ratios (ORs) for the three loci were significant for HSP: HLA-DRB1 01 (OR = 1.805, 95 % CI 1.259-2.588, p = 0.0012); HLA-DRB1 07 (OR = 0.671, 95 % CI 0.469-0.961, p = 0.058); HLA-DRB1 11 (OR = 2.001, 95 % CI 1.50-2.67, p = 0.027). Genetic regulation of endothelial function, such as polymorphisms in genes coding rennin-angiotensin system (RAS) components, endothelial nitric oxide synthases, Inter-Cellular Adhesion Molecule 1, and vascular endothelial growth factor, could also confer effect on HSP. In addition, MEFV, whose mutations cause familial Mediterranean fever, could be an important candidate gene for HSP. Further large studies are required to investigate the association between genetic polymorphisms and HSP. Alternative approaches, such as genome-wide association study, are necessary to help to identify genetic risks for HSP.

MEFV mutations in Iranian Azari Turkish patients with Henoch–Schönlein purpura

“…It is suggested that carrying out more investigations, especially in populations with high prevalence of FMF mutations, would lead to better understanding (4). However, more efforts are necessary to identify the risky patients to implement preventive treatment (4). With regard to these observations, the present study investigated the frequency and clinical significance of MEFV mutations in HSP patients (14).…”

“…HSP is normally described by deposition of immunoglobulin A within the small blood vessel wall (3) and, according to the diagnostic criteria of HSP, this disease would include nonthrombocytopenic palpable purpura and at least one of the other manifestations such as colicky abdominal pain, arthritis, and renal involvement with hematuria and proteinuria, which can progress towards renal failure (1). Although HSP is generally self-limiting and the major pathogenic cause of HSP is still unclear, it seems that inflectional, environmental, and hereditary factors could play important roles in the development and progress of the disease (4).…”

The potential role of HLA-DRB1*11 in the development and outcome of haematopoietic stem cell transplantation-associated thrombotic microangiopathy

“…The association of HLA-DRB1*11 was documented with certain autoimmune, infectious and malignant conditions such as systemic sclerosis, Henoch-Schönlein purpura, Helicobacter pylori-positive idiopathic thrombocytopenic purpura, hairy cell leukaemia, cervical cancer and others. [33][34][35][36][37][38][39][40][41][42] Interestingly, in hairy cell leukaemia, anti-CD22 recombinant immunotoxin BL22-induced haemolytic uraemic syndrome (another, not ADAMTS13 deficiency-associated form of TMA) was also associated with HLA-DRB1*11. 33 The wide clinical spectrum of HLA-DRB1*11-associated conditions advocate the co-occurrence of additional provoking factors, because a unique mechanism is unlikely to drive all the above mentioned conditions.…”

Association of AGT M235T gene polymorphism with HSP/HSPN risk

“…Meta-analysis is a good way to summarize the available evidence to provide a more robust result. Several previous meta-analyses 14,15 reported the association between ACE I/D gene polymorphism and HSP risk. However, the meta-analysis regarding the association between AGT M235T gene polymorphism and HSP/HSPN risk was rare.…”

“…Of these, 70 studies were excluded according to the inclusion and exclusion criteria, five articles 4,[6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] were included in our meta-analysis ( Figure 1). The retrieved data were recorded as follows: first author's surname, publication year, ethnicity, the number of cases and controls.…”