Polymorphism in RANTES chemokine promoter affects extent of sarcoidosis in a Japanese population

Abstract

RANTES, a member of C-C chemokine, is known to be produced at sites of granulomatous reactions in the lung of sarcoidosis. RANTES is a potent eosinophil and lymphocyte attractant with particular preference for CD45RO+ T cells and eosinophils. Polymorphism of the RANTES promoter has recently been shown to be related to allergic and infectious diseases; atopic dermatitis, asthma, and polymyalgia rheumatica. Considering that this might affect sarcoidosis, we studied polymorphism of the RANTES gene in 114 patients with sarcoidosis and 136 healthy control subjects. Their genotypes were determined using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Although no difference in the genotype distribution between healthy control subjects and sarcoidosis patients was identified, the difference in the frequencies of the patients with three or more organ involvement was significant (P<0.01) with the frequency of those in AA genotype being elevated (P<0.05). BAL findings in 48 out of 114 patients who underwent bronchoscopy were reviewed. The CD4/8 ratio of lymphocytes in bronchoalveolar lavage fluid in the patients with AA genotype was significantly increased (P<0.05). From the results, we suggest that in RANTES gene polymorphism the homozygous A allele might be a genetic risk factor for extent disease of sarcoidosis.

RANTES Gene Promoter Polymorphisms Are Associated with Bronchial Hyperresponsiveness in Korean Children with Asthma

“…In our The prevalence of the RANTES -403A or -28 G polymorphisms varied among different ethnic groups. The occurrence of the RANTES -403A allele in our study's Korean children was 42.7%, which correlates well with the results for the Japanese (39.3%) [30] and African-Americans (43%) [15]. This level is higher than that of the Chinese (27%) [17], and significantly higher than that of Caucasian ethnic groups (15-20%) [15].…”

Polymorphisms in CCL2&CCL5 chemokines/chemokine receptors genes and their association with diseases

“…Furthermore, CCL5 over-production correlates with pulmonary sarcoidosis, particularly in patients with more advanced disease 85 . In agreement with this, Takada et al suggested an association of RANTES-403 G/A polymorphism with the number of organs involved and CD4/ CD8 rate, but not with susceptibility to sarcoidosis as a whole 86 .…”

Genetic variants of RANTES are associated with serum RANTES level and protection for type 1 diabetes

“…[5][6][7][8][9][10][11][12] Therefore, RANTES could be considered a gene generally predisposing to autoimmune disease. To test this hypothesis, we investigated RANTES SNPs rs2306630, rs2280788 and rs2107538 in a group of 310 CD patients.…”

“…This gene has not yet been investigated in the context of T1D, although it has been shown to be associated with other autoimmune diseases, such as atopic dermatitis, asthma, sarcoidosis, rheumatoid arthritis and multiple sclerosis. [5][6][7][8][9][10][11][12] RANTES belongs to the family of CC chemokines, which are involved in immunoregulatory and inflammatory processes owing to their ability to recruit, activate and co-stimulate T cells and monocytes. 13,14 In addition to the trafficking effect, RANTES, like other CC chemokines, plays an important role in co-stimulation of T-cell proliferation 15,16 and activation of the T cells localized in the inflammatory lesion.…”