title: Association of CTLA4 gene polymorphisms with lymphatic filariasis in an East Malaysian population.
abstract: Lymphatic filariasis (LF) is a parasitic disease caused by threadlike worms of the Brugia and Wuchereria species that live in the human lymphatic system. Regulatory T cells (Tregs) may play a key role in the pathogenesis of LF, and cytotoxic T-lymphocyte antigen-4 (CTLA4) expressed by Tregs is a potential candidate gene because it modulates T-cell activation. A case-control study was performed to establish a potential association of 5 CTLA4 gene promoter single nucleotide polymorphisms (SNPs; rs733618, rs11571316, rs5742909, rs231775, and rs16840252) with the occurrence of LF in an East Malaysian population (320 LF-infected individuals and 150 healthy controls). Polymorphisms were evaluated using TaqMan real-time polymerase chain reaction followed by direct sequencing. LF carriers of the rs733618 AG genotypes (p = 0.02) and those with combined minor allele G carriers (AG + GG; p = 0.01) exhibited a significantly decreased risk for LF. Among the asymptomatic amicrofilaremic cases, positive associations were reported for all genotypes and variants of rs733618 with odds ratios (ORs) ranging from 0.27 to 0.45. In the asymptomatic microfilaremic cases, marker rs231775 exhibited a significant decreased risk, with ORs ranging from 0.50 to 0.57. The study has identified SNPs in the CTLA4 promoter gene that may be functionally linked with susceptibility to LF.
authors.affiliation: Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Penang, Malaysia.
authors.forename: Zulkarnain Md
authors.initials: ZM
authors.lastname: Idris
authors.forename: Noorizan
authors.initials: N
authors.lastname: Miswan
authors.forename: Jamail
authors.initials: J
authors.lastname: Muhi
authors.forename: Tajul Ariffin Awang
authors.initials: TA
authors.lastname: Mohd
authors.forename: Jürgen F J
authors.initials: JF
authors.lastname: Kun
authors.forename: Rahmah
authors.initials: R
authors.lastname: Noordin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D015703:Antigens, CD / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004605:Elephantiasis, Filarial / Q000235:genetics*; D005091:Exons; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008296:Malaysia; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human