ctla-4 gene variations may influence cervical cancer susceptibility.
BACKGROUND
CTLA-4 is the key player of the immune tolerance. Particular genotypes of ctla-4 have been reported to be associated with various diseases.


OBJECTIVE
We aimed to evaluate the role of four single nucleotide polymorphisms (SNPs) of ctla-4 gene in cervical cancer.


METHODS
55 patients and 110 healthy controls were genotyped for four polymorphic loci, three in promoter region; -1722(T/C), -1661(A/G), -318(C/T) and one in exon 1; +49(A/G) using PCR-ARMS and -RFLP methods.


RESULTS
At position -1661 the frequency of A/A homozygote and A allele were lower in patients than in controls. (P=0.01, P=0.035; respectively), while at position -318 the frequency of C/C homozygote and C allele were increased in patients (P=0.021, P=0.025; respectively). These significances, however, do not stand the Bonferroni correction suggesting that the effect of multiple comparisons should not be ignored. The haplotype analysis demonstrated 9 haplotypes, of which, 5 were observed in both groups with no significant different frequencies. The TGTA haplotype, however, was only observed in control group (9.54%, p=0.002) and the TGCG haplotype was only occurred in cervical cancer patients (6.48%, p=0.0003). The differences were still significant after Bonferroni correction.


CONCLUSIONS
As a conclusion TGTA haplotype as well as A allele at position -1661 might imply a protective role whereas TGCG haplotype as well as C allele at locus -318 might render susceptibility to cervical cancer. Investigation of ctla-4 gene variants in other ethnic populations will consolidate the findings of this study.
Rahimifar
Shahrzad
S
Shiraz Institute for Cancer Research, Shiraz University of Medical Sciences, Shiraz, Iran.
Erfani
Nasrollah
N
Sarraf
Zahra
Z
Ghaderi
Abbas
A
D015703:Antigens, CD / Q000235:genetics*; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D005091:Exons; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D002583:Uterine Cervical Neoplasms / Q000235:genetics*
D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human