Polymorphisms and avascular necrosis in patients with sickle cell disease – A systematic review

Abstract

Objective: To systematically establish whether there is an association between polymorphisms and avascular necrosis in patients with sickle cell disease. Data source: The review, conducted according to PRISMA guidelines and registered with PROSPERO, was based on research of studies in PubMed, SciELO, LILACS, BVS databases and in the gray literature (Google Scholar and Open Gray) published until June 2020. The STROBE initiative was used to analyze the articles’ quality. Data synthesis: Ten articles were selected from the databases and two were included through manual search, totaling 12 studies. All samples gathered 2,362 patients. According to STROBE, seven studies fully and/or partially covered more than 70% of the essential items and two studies reached less than 60%, with an overall variation of 86.4–54.5%. The results indicate that polymorphisms in the genes of the bone morphogenetic protein 6 (BMP6), Klotho (KL) and Annexin A2 (ANXA2) may be associated with osteonecrosis in the context of sickle cell disease. Six articles addressed the polymorphism in the MTHFR enzyme gene, but only one found a positive association. Polymorphisms associated with the DARC receptor, the ITGA4 gene, CD36 and thrombophilia protein genes were not associated in any of the studies. Conclusions: The results indicate that the polymorphisms in BMP6, Klotho and ANXA2 genes may be associated with avascular necrosis in patients with sickle cell disease. However, in order to confirm these genetic changes as risk factors, further studies with greater statistical power and methodological rigor are needed.

Aseptic Osteonecrosis of the Femoral Head in Children Living with Sickle Cell Disease at the National Reference Center for Sickle Cell Disease of Brazzaville, Congo

“…The particularity of our serie is that nearly half of the children were under 11 years old (45.16%), whereas Mouba [13] and Man and Koren [27] reported a prevalence of AOFH clearly greater after the age of 11. The average age is 14 in Brazil and the USA [19,20]. All these results testify to the early onset of this bone complication diagnosed in sometimes young children.…”

“…Akakpo-Numado in Togo reported 14 (including 8 HbSS and 6 HbSC) over a period of 20 years, but these were data from a pediatric surgery department and not from a treatment center for sickle cell disease [14]. The diagnosis was based solely on the realization of a standard X-ray countries where routine radiographic screening for AOFH is carried out in the majority of patients, symptomatic or not: from 9% in the USA(Philadelphia) in the study by Worrall between 0 and 21 years old [19], to 14.13% in Brazil between 0 and 20 years old [20,21]. Still in the USA (New York), Mahadeo reports a prevalence of all genotypes of 12.4% which increases to 14.2% for the HbSS and HbSβ0 thalassemia forms in patients aged 10 to 21 years [22].…”

Polymorphism and Association of the E-selectin and ICAM-1-K469E Genes with Sickle Cell Disease in Congo

“…Although SCD is considered as a monogenic disorder, other host genetic variants might affect specific clinical expression among patients [15]. For example, the Single Nucleotide Polymorphisms (SNP) in the encoding gene of bone morphogenetic protein 6 (BMP6), Klotho (KL), or annexin A2 (ANXA2) have been associated with osteonecrosis in SCD patients [16]. SNPs in the Beta-1 Adrenergic Receptor (ADRB1) gene have been associated with the increased risk of pulmonary hypertension [17].…”

Legg–Calvé–Perthes disease presenting with osteoarthritis: Mechanisms of the development and prospects of conservative therapy using bisphosphonates

“…Обнаружено несколько генов-кандидатов, однонуклеотидные полиморфизмы которых, по мнению ученых, могут играть роль в костном метаболизме и потенцировать риски развития АНГБК. Среди них гены Klotho (KL), BMP6, ANXA2 [19]. За последние несколько лет установлена взаимосвязь гетерозиготной мутации в гене COL2A1 с АНГБК.…”