title: An intronic variable number of tandem repeat polymorphisms of the cold-induced autoinflammatory syndrome 1 (CIAS1) gene modifies gene expression and is associated with essential hypertension.
abstract: Cold-induced autoinflammatory syndrome 1 (CIAS1) gene is a member of the NALP subfamily of the CATERPILLER protein family that is expressed predominantly in peripheral blood leukocytes, which is to regulate apoptosis or inflammation through the activation of NF-kappaB and caspase. Recent genetic analyses suggested an association between inflammation and oxidative stress-related genes in the development of hypertension. This is the first genetic study indicating an association between the CIAS1 gene and susceptibility to essential hypertension (EH). The frequency of subject with the homozygote of 12 repeat allele was significantly higher in patients with hypertension compared with control subjects (987 cases, 924 controls) (P=0.030; odds ratio=1.24) at a novel VNTR polymorphism of CIAS1 intron 4 loci. We also found that the mean of systolic blood pressure of homozygotes of 12 repeat allele was 6.4 mmHg higher than those of homozygotes of non-12 repeat allele in male random population (P=0.009). The frequency of six SNPs spanning of the CIAS1 gene was not significantly between patients and controls. The real-time PCR analysis showed that among healthy young adults, 12-12 subjects expressed CIAS1 mRNA in peripheral leukocytes significantly more abundantly than homozygote of non-12 repeat alleles subjects (P<0.05). Reporter gene assay of the CIAS1-VNTR in HL60 stimulated by lipopolysaccharides showed that the intronic sequence involving 12 repeat increased the expression of luciferase compared with 9, 7, and 6 repeats. Thus, we propose here the CIAS1 is associated with EH through the dominant expression of transcripts, which may depend on the CIAS1-VNTR genotype.
authors.affiliation: Division of Human Genetics, Center for Community Medicine, Jichi Medical School, Minamikawachi-machi, Tochigi 329-0498, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Omi
authors.forename: Maki
authors.initials: M
authors.lastname: Kumada
authors.forename: Toyomi
authors.initials: T
authors.lastname: Kamesaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Okuda
authors.forename: Lkhagvasuren
authors.initials: L
authors.lastname: Munkhtulga
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Yanagisawa
authors.forename: Nanami
authors.initials: N
authors.lastname: Utsumi
authors.forename: Takaya
authors.initials: T
authors.lastname: Gotoh
authors.forename: Akira
authors.initials: A
authors.lastname: Hata
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Soma
authors.forename: Satoshi
authors.initials: S
authors.lastname: Umemura
authors.forename: Toshio
authors.initials: T
authors.lastname: Ogihara
authors.forename: Norio
authors.initials: N
authors.lastname: Takahashi
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Tabara
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Shimada
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mano
authors.forename: Eiji
authors.initials: E
authors.lastname: Kajii
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Miki
authors.forename: Sadahiko
authors.initials: S
authors.lastname: Iwamoto
mesh_terms: D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D007438:Introns / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D020080:Tandem Repeat Sequences / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human