Biology Reference
In-Depth Information
coding variant Thr9Ile (T9I, rs1805388) in the LIG4 was significantly
associated (p
0.024) with specific IgE levels to Ascaris in a population
of 1064 individuals from Cartagena, Colombia. Bioinformatic anal-
ysis using the PolyPhen-2 program
61
to assess the likely functional
effect expected of this non-synonymous variant predicts that
¼
this
variant is possibly damaging (PolyPhen-2 score
0.520). However, in
the Jirel sample, we find that there is no relationship between this
variant and Ascaris burden (p
¼
0.818) which suggests that it is unlikely
to be a cause of the original QTL. Acevedo et al.
60
also identified an
intronic TNFSF13B variant (rs10508198) that was not associated with
Ascaris-specific IgE, but was strongly associated (p
¼
0.003) with IgG
levels specific to Ascaris. We currently have no information on this
variant in our study of the Jirels. Additionally, this group of investi-
gators found no significant association with a 3
0
UTR variant near the
IRS2 gene.
60
With regard to other genomic regions, Ramsay and colleagues
62
assessed the potential association of the
¼
b
2
-adrenergic receptor (ADRB2)
gene with Ascaris infection as part of their studies of asthma in a Ven-
ezuelan population. They examined two coding variants, Gly16Arg
(G16R, rs1042713) and Glu27Gln (E27Q, rs1042714), in this gene and
genotyped 126 children from Coche Island who were also characterized
for levels of Ascaris infection. The results of this study indicated that
children who were homozygous for Arg16 had significantly higher
Ascaris egg counts (p
0.001) than children who were not homozygous
for the allele. The gene was also associated with significantly higher
levels of Ascaris specific IgE (p
<
0.002). PolyPhen-2 analysis predicts
that both the R16G variant (PolyPhen-2 score
¼
¼
0.043) and the E27Q
variant (PolyPhen-2 score
0.009) are most likely to be benign (sug-
gesting little alteration of the functional capacity of the protein).
Consistent with this bioinformatic prediction, both of these variants are
available in our Jirel sample and neither show any relationship to
Ascaris egg counts (R16G, p
¼
0.071). These results
suggest that it is unlikely these variants are directly influencing infec-
tion levels.
Finally, a study in China has assessed the association between
variants in a number of genes relatedtotheTh-2andTh-1immune
cytokine signaling pathway that have been previously associated with
asthma and Ascaris infection in children. Utilizing data from 614
children, they determined that a variant (G4219A, rs324015) of the
STAT6 gene was significantly associated (p
¼
0.904; E27Q, p
¼
¼
0.001) with low Ascaris
egg counts.
63
However, when we examine our Jirel-derived data for
this gene, we do not observe any significant association with Ascaris
egg counts for this marker (p
¼
0.309) or any other marker in or near
this gene.
