Association of a PD-L2 gene polymorphism with chronic lymphatic filariasis in a South Indian cohort

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Item Type:	Article
Title:	Association of a PD-L2 gene polymorphism with chronic lymphatic filariasis in a South Indian cohort
Creators Name:	Venugopal, G., O'Regan, N.L., Babu, S., Schumann, R.R., Srikantam, A., Merle, R., Hartmann, S. and Steinfelder, S.
Abstract:	Lymphatic filariasis (LF) is a parasitic infection, caused by three closely related nematodes, namely Wuchereria bancrofti, Brugia malayi, and Brugia timori. Previously, we have shown that lysate from B. malayi microfilariae induces the expression of interleukin (IL)-10 and programmed death-ligand (PD-L) 1 on monocytes, which lead to inhibition of CD4+ T-cell responses. In this study, we investigated associations of IL-10 and programmed cell death (PD)-1 pathway gene polymorphisms with clinical manifestation in LF. We evaluated the frequency of alleles and genotypes of IL-10 (rs3024496, rs1800872), IL-10RA (rs3135932), IL-10RB (rs2834167), PD-1 (rs2227982, rs10204525), PD-L1 (rs4143815), PD-L2 (rs7854413), and single-nucleotide polymorphisms (SNPs) in 103 patients with chronic pathology (CP), such as elephantiasis or hydrocele and 106 endemic normal (EN) individuals from a South Indian population living in an area endemic for LF. Deviations from the Hardy-Weinberg equilibrium were tested, and we found a significant difference between the frequency of polymorphisms in PD-L2 (rs7854413; P < 0.001) and IL-10RB (rs2834167; P = 0.012) between the CP and the EN group, whereas there were no significant differences found among IL-10, IL-10RA, PD-1, and PD-L1 SNPs. A multivariate analysis showed that the existence of a CC genotype in PD-L2 SNP rs7854413 is associated with a higher risk of developing CP (OR: 2.942; 95% confidence interval [CI]: 0.957-9.046; P = 0.06). Altogether, these data indicate that a genetically determined individual difference in a non-synonymous missense SNP of PD-L2 might influence the susceptibility to CP.
Keywords:	Alleles, B7-H1 Antigen, Brugia, Brugia Malayi, Chronic Disease, Filarial Elephantiasis, Gene Expression, Gene Frequency, Genetic Predisposition to Disease, Host-Parasite Interactions, India, Interleukin-10, Interleukin-10 Receptor beta Subunit, Prevalence, Programmed Cell Death 1 Ligand 2 Protein, Programmed Cell Death 1 Receptor, Protein Isoforms, Single Nucleotide Polymorphism, Animals, Wuchereria bancrofti
Source:	American Journal of Tropical Medicine and Hygiene
ISSN:	0002-9637
Publisher:	American Society of Tropical Medicine and Hygiene
Volume:	100
Number:	2
Page Range:	344-350
Date:	February 2019
Official Publication:	https://doi.org/10.4269/ajtmh.18-0731
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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