Interleukin (IL)-12 receptor beta1 codon 378 G homozygote and allele, but not IL-1 (beta-511 promoter, 3953 exon 5, receptor antagonist), IL-2 114, IL-4-590 intron 3, IL-8 3'-UTR 2767, and IL-18 105, are associated with higher susceptibility to leiomyoma.
OBJECTIVE
To investigate whether certain polymorphisms are correlated with leiomyoma susceptibility, i.e., interleukin (IL)-1, IL-2, IL-4, IL-8, IL-12, and IL-18, which are all immunomodulatory cytokines that play important roles in host immune responses against cancers.


METHODS
Departments of gynecology and genetics in a medical center.


METHODS
Women were divided into: [1] a leiomyoma group (n = 162) and [2] a nonleiomyoma group (n = 156).


METHODS
Genotyping for the IL-1beta-511 promoter, IL-1beta exon 5, IL-1Ra, IL-2 114, IL-4 -590 intron 3, IL-8 3'-UTR 2767, IL-12Rbeta1 codon 378, and IL-18 105 were evaluated by polymerase chain reaction-restriction fragment length polymorphism.


METHODS
Genotypes and allelic frequencies in both groups were compared.


RESULTS
Proportions of IL-12Rbeta1 codon 378 *CC/CG/GG in the leiomyoma and nonleiomyoma groups were: [1] 7.4%/43.8%/48.8% and [2] 11.5%/54.5%/34%, respectively. Distributions of other polymorphisms in both groups were not significantly different. Proportions of IL-1beta-511 promoter *CC/CT/TT were: [1] 22.8%/50%/27.2% and [2] 21.8%/57.1%/21.1% in the leiomyoma and nonleiomyoma groups, respectively. The IL-1beta exon 5 *E1 homozygote/heterozygote/E2 homozygote were: [1] 96.3%/3.7%/0% and [2] 96.9%/3.1%/0% in the leiomyoma and nonleiomyoma groups, respectively. Alleles I/II/III/IV/V for IL-1Ra were: [1] 92.6%/7.1%/0.3%/0/0% and [2] 93.9%/5.7%/0%/0.4/0% in the leiomyoma and nonleiomyoma groups, respectively. The IL-2 114 G homozygote/heterozygote/T homozygote were: [1] 27.8%/49.4%/22.8% and [2] 20.5%/53.2%/26.3% in the leiomyoma and nonleiomyoma groups, respectively. The IL-4 -590 intron 3 *RP1 homozygote/heterozygote/RP2 homozygote were: [1] 64.8%/32.7%/2.5% and [2] 69.2%/26.9%/3.9% in the leiomyoma and nonleiomyoma groups, respectively. The IL-8 3'-UTR 2767 A homozygote/heterozygote/G homozygote were: [1] 14.2%/43.8%/42% and [2] 20.5%/41.7%/37.8% in the leiomyoma and nonleiomyoma groups, respectively. The IL-18 *AA/AC/CC were: [1] 56.8%/40.7%/2.5% and [2] 59%/39.7%/1.3% in the leiomyoma and nonleiomyoma groups, respectively.


CONCLUSIONS
The IL-12Rbeta1 codon 378 *G homozygote and G allele are related to a higher susceptibility to leiomyoma. The IL-1beta-511 promoter, IL-1beta exon 5, and IL-1Ra, IL-2 114, IL-4 -590 intron 3, IL-8 3'-UTR 2767, and IL-18 105 gene polymorphisms are not correlated with the development of leiomyoma.
Hsieh
Yao-Yuan
YY
Department of Obstetrics and Gynecology, National Chiao Tung University, Hsinchu, Taiwan.
Chang
Chi-Chen
CC
Tsai
Chang-Hai
CH
Lin
Cheng-Chieh
CC
Tsai
Fuu-Jen
FJ
D020413:3' Untranslated Regions; D003062:Codon; D005091:Exons; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000502:physiology; D020382:Interleukin-18 / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics*; D007376:Interleukin-2 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D007889:Leiomyoma / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D053707:Receptors, Interleukin-12 / Q000235:genetics*; D014594:Uterine Neoplasms / Q000235:genetics* / Q000276:immunology
D020413:3' Untranslated Regions; D003062:Codon; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D020382:Interleukin-18; D053583:Interleukin-1beta; D007376:Interleukin-2; D016209:Interleukin-8; D053707:Receptors, Interleukin-12; D015847:Interleukin-4