Association of a PD-L2 Gene Polymorphism with Chronic Lymphatic Filariasis in a South Indian Cohort

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.

Relationship between CD274 gene polymorphism and systemic lupus erythematosus risk in a Chinese Han population

“…36 For patients with chronic lymphatic filariasis, rs4143815 showed no difference in genotype distribution between patients and healthy controls in the south Indian population. 37 In the present study, the frequencies of CC genotype and C allele at the rs4143815 locus were found to be significantly lower in SLE patients than in healthy controls, suggesting that the rs4143815 polymorphism is associated with lower risk of SLE in the Chinese Han population and may be a protective factor for SLE development. This study also showed that GA genotype at the rs822339 locus may be associated with risk of developing SLE, and frequency of GA genotype was higher in SLE patients than in healthy controls, suggesting that the rs822339 GG genotype may be negatively associated with the risk of developing SLE.…”

“…In a Polish study of non‐small cell lung cancer, a higher frequency of CC genotype at the rs4143815 locus in the patient group than in healthy controls was noted (OR = 2.31) 36 . For patients with chronic lymphatic filariasis, rs4143815 showed no difference in genotype distribution between patients and healthy controls in the south Indian population 37 . In the present study, the frequencies of CC genotype and C allele at the rs4143815 locus were found to be significantly lower in SLE patients than in healthy controls, suggesting that the rs4143815 polymorphism is associated with lower risk of SLE in the Chinese Han population and may be a protective factor for SLE development.…”

Programmed Death Ligand 2 Gene Polymorphisms Are Associated With Lung Adenocarcinoma Risk in Female Never-Smokers

“…Among the 12 PDCD1LG2 SNPs, the clinical significance of rs7854413 was the most commonly reported in the previous literatures. A cohort study in south India reported that patients with the PDCD1LG2 SNP rs7854413 and lymphatic filariasis infection were susceptible to chronic lymphatic pathologies (40), and rs7854413 polymorphism was related to advanced fibrosis and development of hepatocellular carcinoma from patient with non-alcoholic steatohepatitis (41). Notably, rs7854413 was also associated with recurrence in patients with early-stage NSCLC (42).…”

The Genetic Polymorphisms of 24 Base Pair Duplication and Point G102S of Human Chitotriosidase to Bancroftian Filariasis at the Thai–Myanmar Border

“…The variability of prevalence and clinical outcomes of lymphatic filariasis are affected by socioeconomic status, personal activities, age, gender and host genetics [2,3,4]. The polymorphisms of host defense pathway genes, including MBL , VEGF , HLA , TLR , PDL-1i and IL-10RB are associated with susceptibility and clinical status of the disease [5,6,7,8,9,10].…”

“…Several studies have demonstrated the association of polymorphisms of host defense pathway genes with susceptibility and clinical outcomes of bancroftian filariasis (BF). Polymorphisms of mannose-binding lectin ( MBL ), vascular endothelial growth factor ( VEGF ), human leukocyte antigen ( HLA ), toll-like receptor ( TLR ), programmed cell death-1 ( PDL-1 ), interleukin-10 ( IL-10RB ) and chitotriosidase ( CHIT1 ) increase susceptibility to BF [5,6,7,8,9,10].…”