Haptoglobin polymorphism and bronchial asthma

Margarida Cortez, Andreia Matos, Joana Ferreira and Manuel Bicho

Asthma is considered a heterogeneous disease, characterized most of the times by a Th2 inflammatory response. Haptoglobin (Hp), is an alfa2-sialoglycoprotein known to bind free hemoglobin (Hb) and has been implicated in modulation of Th1/Th2 response, Intervening in innate and adaptive immune response. The Hp locus is situated at 16q22 chromosome, being in humans, polymorphic for the α chain. The α chain of Hp has 2 major co-dominant alleles Hp*1 and Hp*2, with 3 genotype variants, Hp1-1, Hp2-1, Hp2-2. The aim of the study is to establish a relation between Hp genotypes and Hp levels (intermediate phenotype), and the pathophysiology of asthma when compared with a control group of healthy blood donors. In a group of 114 asthmatic patients and 50 controls we studied the Hp levels that were determined by nephelometry and genotypes by polyacrylamide gel electrophoresis (PAGE). Statistical analysis was performed with statistical software PASW version 18, having established a level of significance of p< 0.05.

We found that Allelic (Hp*1 e Hp*2) and Hp genotypes (Hp 1-1, Hp 2-1, Hp 2-2) distribution in asthmatics, are not statistical different from control group (p> 0.05). There is no statistical differences in the asthmatics between, gender, age-group, atopics and non-atopics, controlled and non-controlled asthma (p>0, 05). The different genotypes seem not to be related with an increased risk of having asthma when compared with the control group (p>0, 05). In control group there is no statistical differences in Hp levels by genotype and age- group (p>0, 05). When we compare asthmatics with control group we verified that in asthma , the levels of Hp are always lower than in the control group (125,13±50,95vs137,86±51,39mg/dL) and there was a statistical difference in Hp2-2 genotype (95,60±41,43 vs 128, 40±51,48mg/dL) (p<0, 05). In asthmatics Hp levels, are statistical different between ages >30 years and <15 years (135.6±50.05 vs 87.45± 38.89 mg/dL) (p<0.05). In asthmatics Hp levels, present statistical differences by genotype (p=0,000). Those who express Hp 2-2 had the lower levels of the circulating protein when compared with Hp 2-1 and Hp 1-1(95,6 ± 41,93 vs 137,37±49,58 vs 146,09±47,37mg/dL) ,and it is statistical different (p=0.000 ).In those asthmatics with age ≥15 years Hp levels are different by genotype (p<0.05): 1-1 and 2-1 differ from 2-2. Those patients with age <15 years, Hp levels were no different between genotypes (p>0, 05). In a pos-Hoc analysis Hp 2-2 is an independent factor, as age <15 years, associated with lower levels of Hp.

Although no statistical differences were find between Hp genotype and allelic distribution in the group of asthmatics when compared to control group we verified that asthmatics had lower levels of the circulating Hp when compared to the control- group and that this difference is associated with Hp 2-2 genotype. In asthmatics, Hp levels are different between genotypes (with age ≥15 years) because Hp levels are lower in the Hp2-2 genotype when compared with the other genotypes.In the future, studies done with Hp should be controlled by age , because the Hp levels are lower in the pediatric group. These data point to differences among groups that could be related to Hp genotypes, and possibly with different immunological profiles.

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