KYNU gene variants and lifestyle factors associated with Asthma in Singapore Chinese.

Abstract

<b>Background:</b> Asthma is a complex disease with many genes and environmental factors playing a role. The current study aims to understand the role played by the gene “KYNU”, along with relevant lifestyle factors. <b>Methods:</b> Allergic Asthma cases (n=1163) and Atopic controls (n=1992) were genotyped. Expression of KYNU promoter variants was measured using luciferase assay in HEK293T cells. RNA-Seq data from PBMC’s (n=278) was then used for correlations between KYNU and enzymes synthesising Vitamin B6(B6). Participant questionnaires were used for testing associations between asthma and lifestyle factors. <b>Results:</b> KYNU variant “GCCGA” was found to increase the risk for asthma (OR=1.05, 95%CI=1.01-1.08, p=0.003) compared to other variants. Based on KYNU’s location in the “kynurenine pathway”, low levels of KYNU can lead to asthma. This was tested using luciferase assay, where the transcription activity of “GCCGA” was found lower compared to others(p&lt;0.05). B6 was already known to act as a cofactor for KYNU. We tried to further verify this by looking at correlations between PDXK and PNPO— enzymes synthesising B6—and KYNU, and found them significant (p=2.75e-18, p=4.26e-22). Confirming B6 as a cofactor for KYNU, we then hypothesised that lifestyle factors lowering B6 should be associated with asthma as well and tested this by looking at factors known to lower B6 levels – alcohol intake and High Glycemic Index (GI) food— and found higher asthma risk in frequent drinkers compared to sober (p&lt;0.01). Further, Low GI food was found protective for asthma (OR=0.722, 95%CI=0.607-0.895). <b>Conclusion:</b> KYNU variants, frequent alcohol intake and High GI food, all seem to increase the risk of asthma, probably via the same pathway.