TY - JOUR
T1 - Differences in genetic variation in antigen-processing machinery components and association with cervical carcinoma risk in two Indonesian populations
AU - Mehta, Akash M.
AU - Spaans, Vivian M.
AU - Mahendra, Nyoman Bayu
AU - Osse, Elisabeth M.
AU - Vet, Jessica N.I.
AU - Purwoto, Gatot
AU - Surya, I. G.D.
AU - Cornian, Santoso
AU - Peters, Alexander A.
AU - Fleuren, Gert J.
AU - Jordanova, Ekaterina S.
N1 - Publisher Copyright:
© 2015, The Author(s).
PY - 2015/6/15
Y1 - 2015/6/15
N2 - Genetic variation of antigen-processing machinery (APM) components has been shown to be associated with cervical carcinoma risk and outcome in a genetically homogeneous Dutch population. However, the role of APM component single nucleotide polymorphisms (SNPs) in genetically heterogeneous populations with different distributions of human papillomavirus (HPV) subtypes remains unclear. Eleven non-synonymous, coding SNPs in the TAP1, TAP2, LMP2, LMP7 and ERAP1 genes were genotyped in cervical carcinoma patients and healthy controls from two distinct Indonesian populations (Balinese and Javanese). Individual genotype and allele distributions were investigated using single-marker analysis, and combined SNP effects were assessed by haplotype construction and haplotype interaction analysis. Allele distribution patterns in Bali and Java differed in relation to cervical carcinoma risk, with four ERAP1 SNPs and one TAP2 SNP in the Javanese population showing significant association with cervical carcinoma risk, while in the Balinese population, only one TAP2 SNP showed this association. Multimarker analysis demonstrated that in the Javanese patients, one specific haplotype, consisting of the ERAP1-575 locus on chromosome 5 and the TAP2-379 and TAP2-651 loci on chromosome 6, was significantly associated with cervical carcinoma risk (global P = 0.008); no significant haplotype associations were found in the Balinese population. These data indicate not only that genetic variation in APM component genes is associated with cervical carcinoma risk in Indonesia but also that the patterns of association differ depending on background genetic composition and possibly on differences in HPV type distribution.
AB - Genetic variation of antigen-processing machinery (APM) components has been shown to be associated with cervical carcinoma risk and outcome in a genetically homogeneous Dutch population. However, the role of APM component single nucleotide polymorphisms (SNPs) in genetically heterogeneous populations with different distributions of human papillomavirus (HPV) subtypes remains unclear. Eleven non-synonymous, coding SNPs in the TAP1, TAP2, LMP2, LMP7 and ERAP1 genes were genotyped in cervical carcinoma patients and healthy controls from two distinct Indonesian populations (Balinese and Javanese). Individual genotype and allele distributions were investigated using single-marker analysis, and combined SNP effects were assessed by haplotype construction and haplotype interaction analysis. Allele distribution patterns in Bali and Java differed in relation to cervical carcinoma risk, with four ERAP1 SNPs and one TAP2 SNP in the Javanese population showing significant association with cervical carcinoma risk, while in the Balinese population, only one TAP2 SNP showed this association. Multimarker analysis demonstrated that in the Javanese patients, one specific haplotype, consisting of the ERAP1-575 locus on chromosome 5 and the TAP2-379 and TAP2-651 loci on chromosome 6, was significantly associated with cervical carcinoma risk (global P = 0.008); no significant haplotype associations were found in the Balinese population. These data indicate not only that genetic variation in APM component genes is associated with cervical carcinoma risk in Indonesia but also that the patterns of association differ depending on background genetic composition and possibly on differences in HPV type distribution.
KW - Antigen-processing machinery
KW - Cervical carcinoma
KW - Genetic variation
KW - Haplotype interaction
KW - Human papilloma virus
KW - Indonesia
KW - Single nucleotide polymorphisms
UR - http://www.scopus.com/inward/record.url?scp=84939976181&partnerID=8YFLogxK
U2 - 10.1007/s00251-015-0834-5
DO - 10.1007/s00251-015-0834-5
M3 - Article
C2 - 25796583
AN - SCOPUS:84939976181
SN - 0093-7711
VL - 67
SP - 267
EP - 275
JO - Immunogenetics
JF - Immunogenetics
IS - 5-6
ER -
