Variants in the non-coding region of the TLR2 gene associated with infectious subphenotypes in pediatric sickle cell anemia

Susana David, Pedro Aguiar, Liliana Antunes, Alexandra Dias, Anabela Morais, Anavaj Sakuntabhai, João Lavinha

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Sickle cell anemia (SCA) is characterized by chronic hemolysis, severe vasoocclusive crises (VOCs), and recurrent often severe infections. A cohort of 95 SCA pediatric patients was the background for genotype-to-phenotype association of the patient’s infectious disease phenotype and three non-coding polymorphic regions of the TLR2 gene, the −196 to −174 indel, SNP rs4696480, and a (GT)n short tandem repeat. The infectious subphenotypes included (A) recurrent respiratory infections and (B) severe bacterial infection at least once during the patient’s follow-up. The absence of the haplotype [Del]-T-[n ≥ 17] (Hap7) in homozygocity protected against subphenotype (B), in a statistically significant association, resisting correction for multiple testing. For the individual loci, the same association tendencies were observed as in the haplotype, including a deleterious association between the SNP rs4696480 T allele and subphenotype (A), whereas the A/A genotype was protective, and a deleterious effect of the A/T genotype with subphenotype (B), as well as including the protective effect of −196 to −174 insert (Ins) and deleterious effect of the deletion (Del) in homozygocity, against subphenotype (B). Moreover, a reduction in the incidence rate of severe bacterial infection was associated to a rise in the hemolytic score, fetal hemoglobin levels (prior to hydroxyurea treatment), and 3.7-kb alpha-thalassemia. Interestingly, differences between the effects of the two latter covariables favoring a reduction in the incidence rate of subphenotype (B) contrast with a resulting increase in relation to subphenotype (A). These results could have practical implications in health care strategies to lower the morbidity and mortality of SCA patients.

Original languageEnglish
Pages (from-to)37-51
JournalImmunogenetics
Volume70
Issue number1
DOIs
Publication statusPublished - 2018

Fingerprint

Sickle Cell Anemia
Pediatrics
Bacterial Infections
Haplotypes
Genes
Single Nucleotide Polymorphism
Genotype
alpha-Thalassemia
Fetal Hemoglobin
Hydroxyurea
Incidence
Genetic Association Studies
Hemolysis
Respiratory Tract Infections
Microsatellite Repeats
Communicable Diseases
Alleles
Morbidity
Delivery of Health Care
Phenotype

Keywords

  • Genetic variants
  • Genotype-to-phenotype association
  • Hemolytic component
  • Sickle cell anemia
  • TLR2
  • Viral and bacterial infection

Cite this

David, Susana ; Aguiar, Pedro ; Antunes, Liliana ; Dias, Alexandra ; Morais, Anabela ; Sakuntabhai, Anavaj ; Lavinha, João. / Variants in the non-coding region of the TLR2 gene associated with infectious subphenotypes in pediatric sickle cell anemia. In: Immunogenetics. 2018 ; Vol. 70, No. 1. pp. 37-51.
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Variants in the non-coding region of the TLR2 gene associated with infectious subphenotypes in pediatric sickle cell anemia. / David, Susana; Aguiar, Pedro; Antunes, Liliana; Dias, Alexandra; Morais, Anabela; Sakuntabhai, Anavaj; Lavinha, João.

In: Immunogenetics, Vol. 70, No. 1, 2018, p. 37-51.

Research output: Contribution to journalArticle

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AU - David, Susana

AU - Aguiar, Pedro

AU - Antunes, Liliana

AU - Dias, Alexandra

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AU - Sakuntabhai, Anavaj

AU - Lavinha, João

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