Association of <i>HMIP1</i> C-893A polymorphism and disease severity in patients with sickle cell anemia

Pereira-Martins, Diego A; Domingos, Igor F; Belini-Junior, Edis; Coelho-Silva, Juan L; Weinhäuser, Isabel; Araújo, Aderson S; Lobo, Clarisse L; Bonini-Domingos, Claudia R; Bezerra, Marcos A; Lucena-Araujo, Antonio R

doi:10.1016/j.htct.2020.03.006

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Hematology, Transfusion and Cell Therapy

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Original article • Hematol., Transfus. Cell Ther. 43 (03) • Jul-Sep 2021 • https://doi.org/10.1016/j.htct.2020.03.006 copy

Association of HMIP1 C-893A polymorphism and disease severity in patients with sickle cell anemia

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Introduction:

Sickle cell anemia (SCA) is a Mendelian disorder with a heterogeneous clinical course. The reasons for this phenotypic diversity are not entirely established, but it is known that high fetal hemoglobin levels lead to a milder course of the disease. Additionally, genetic variants in the intergenic region HBS1L-MYB promote high levels of fetal hemoglobin into adulthood.

Objective:

In the present study, we investigated the HMIP1 C-839A (rs9376092) polymorphism, located at the HBS1L-MYB intergenic region block 1, in SCA patients.

Method:

We analyzed 299 SCA patients followed in two reference centers in Brazil. The HMIP1 C-839A (rs9376092) genotypes were determined by allele specific polymerase chain reactions. Clinical and laboratory data were obtained from patient interviews and medical records.

Results:

The median fetal hemoglobin levels were higher in patients with the HMIP1 C-839A (rs9376092) AA genotype (CC = 6.4%, CA = 5.6% and AA = 8.6%), but this difference did not reach significance (p = 0.194). No association between HMIP1 C-839A (rs9376092) genotypes and other clinical and laboratorial features was detected (p > 0.05).

Conclusion:

In summary, our data could not support the previously related association between the HMIP1 C-893A (rs9376092) polymorphism and differential fetal hemoglobin levels.

Keywords:
Sickle cell anemia; HBS1L-MYB polymorphisms; Fetal hemoglobin; Clinical outcome

	All (n = 299		CC (n = 223)		CA (n = 67) %		AA (n = 9)		p-Value
	No.	%	No.	%	No.	%	No.	%	p-Value
Gender					0.422
Female	173	57.9	126	56.5	40	59.7	7	77.8
Male	126	42.1	97	43.5	27	40.3	2	22.2
Age (years), median	30		30		30		42		0.667
Range	18–63		18–63		19–61		18–55
Fetal hemoglobin (%), median	6.3		6.4		5.6		8.6		0.194
Range	0.5–35.4		0.5–35.4		0.5–23.4		5.8–16.7
Hemoglobin (g/dl), median	7.9		7.9		8.0		8.4		0.962
Range	4.2–11.5		4.2–11.3		5.4–11.5		5.6–9.9
WBC (×10⁹9 Akinsheye I, Alsultan A, Solovieff N, Ngo D, Baldwin CT, Sebastiani P, et al. Fetal hemoglobin in sickle cell anemia. Blood [Internet]. 2011;118(July (1)):19–27. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21490337 http://www.ncbi.nlm.nih.gov/pubmed/21490... /L), median Range	10.8 3.7–29.1		10.9 3.7–29.1		10.6 4.8–22.6		8.8 7.3–18.8		0.613
Platelet count (×10⁹9 Akinsheye I, Alsultan A, Solovieff N, Ngo D, Baldwin CT, Sebastiani P, et al. Fetal hemoglobin in sickle cell anemia. Blood [Internet]. 2011;118(July (1)):19–27. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21490337 http://www.ncbi.nlm.nih.gov/pubmed/21490... /L), median Range	433 143–821		426 143–814		450 235–821		415 240–544		0.829
Reticulocyte count (%), median	9.8		9.5		10.0		9.0		0.916
Range	2.0–26.7		2.2–26.7		2.6–19.6		2.0–13.2
Lactate dehydrogenase (U/L), median	945		928		1020	896	0.931
Range	195–5504		195–4725		267–5504	692–1680
Indirect bilirubin (mg/dL), median	3.0		3.0		3.1	2.6	0.390
Range	1.8–11.6		1.8–9.6		1.8–11.6	1.8–3.7
Number of VOC per year ^a a We only considered the number of VOC documented in the last year (2016).									0.260
0–2	202	67.6	144	64.6	50	74.6	8	88.9
3–6	77	25.7	61	27.3	15	22.4	1	11.1
>6	20	6.7	18	8.1	2	3.0	0	0.0
Leg ulcers									0.693
Yes	94	31.4	69	30.9	21	31.3	4	44.4
No	205	68.6	154	69.1	46	68.7	5	55.6
Osteonecrosis									0.369
Yes	30	10.0	23	10.3	5	7.5	2	22.2
No	269	90.0	200	89.7	62	92.5	7	77.8
Stroke									0.320
Yes	21	7.0	18	8.1	2	3.0	1	11.1
No	278	93.0	205	91.9	65	97.0	8	88.9
Priapism ^b b Only male patients were considered.									0.672
Yes	30	23.8	23	23.7	6	22.2	1	50.0
No	96	76.2	74	76.3	21	77.8	1	50.0
Number of complications ^c c It was considered as complications: leg ulcer, osteonecrosis, stroke and priapism. Patients assigned as “None” were those who did not experience the aforementioned clinical events.									0.084
None	112	37.5	75	33.6	34	50.7	3	33.4
1	109	36.4	87	39.0	20	29.9	2	22.2
2–4	78	26.1	61	27.4	13	19.4	4	44.4

Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH) R. Dr. Diogo de Faria, 775 cj 133, 04037-002, São Paulo / SP - Brasil - São Paulo - SP - Brazil
E-mail: htct@abhh.org.br

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[1] *Corresponding author at: Genetics Postgraduate Program, Universidade Federal de Pernambuco (UFPE), Av. Prof. Moraes Rego, 1235, Recife, PE 50670-901, Brazil. Tel: +55 81 2126 7825; Fax: +55 81 2126 7825. E-mail address: domingos if@hotmail.com (I.F. Domingos).