Gender differences in gene polymorphisms are linked to up-reguated leukotriene pathway in asthma

Abstract

<b>Background:</b> Single nucleotide polymorphisms (SNPs) of the leukotriene (LT) pathway might represent a risk factor for many inflammatory diseases associated with LT production. The 5-lipoxygenase protein enzyme (5-LO) and its downstream LT metabolites are important modulators of inflammation in asthma, but whether gender differences underlie the different phenotypes observed in males (M) and females (F) is unknown. <b>Aims and objectives:</b> We investigated the gender-associated genetic variations of Arachidonate 5-lipoxygenase (ALOX-5), encoding for 5-LO, and the ALOX-5 activating protein (AP), encoding for the 5-lipoxygenase-activating protein (FLAP), in M and F from a clinical well-characterized patient cohort. <b>Methods:</b> In a prospective cohort of 158 age- and sex-matched subjects with asthma and healthy controls, three SNPs involved in LTs pathway were genotyped with allele-specific rtPCR from dry buccal swab samples. Also, serum levels of 5-LO were measured by ELISA. <b>Results:</b> Homozygous variant allele of ALOX5 rs2029253 and rs2115819 were more frequent in M compared to F (p&lt; 0.0001) and were associated with lower levels of 5-LO (p&lt; 0.0001) in M. Instead, F with the ALOX-5 homozygous variant allele rs2029253 had higher levels of 5-LO (p&lt;0.0001). Moreover, the ALOX5AP homozygous wildtype allele rs10507391 was more frequent in F compared to M (p &lt; 0.05). <b>Conclusions:</b> Our results point at gender-associated genetic polymorphisms associated with increased levels of asthma inflammatory markers. The characterization of such genetic polymorphisms in M and F may represent a new resource in the prediction of drug responses and clinical outcomes in asthma with a gender-informed approach.