Publications

BACKGROUND

Patients with chronic kidney disease manifest an inflammatory state relative to healthy individuals. Inflammation is regulated in part by genes of the interleukin-1 (IL-1) gene cluster. We hypothesized that polymorphisms in this gene cluster may be associated with risk of end-stage renal disease (ESRD).

METHODS

Polymorphisms in the IL-1 gene cluster were examined in a cohort of 239 racially diverse hemodialysis (HD) patients and 252 controls. These individuals were genotyped for 3 single nucleotide polymorphisms (SNPs) in the IL-1alpha and beta genes, and a variable-number-of-tandem-repeats polymorphism in the IL-1 receptor antagonist gene (IL-1RN). Polymorphisms were analyzed by logistic regression for their independent associations with ESRD, and the effect of allele dose of IL-1RN on risk for ESRD was examined. The interaction between race and genotype was also investigated.

RESULTS

A logistic regression model demonstrated that homozygosity for allele 2 of the IL-1RN variable-number-of-tandem-repeats (VNTR) polymorphism was associated with ESRD independent of race (P < 0.0005). The IL-1alpha-889 promoter SNP was associated with ESRD independent of race and of the IL-1RN polymorphism (P= 0.04). The IL-1beta-511 promoter SNP is associated with ESRD, but this is accounted for by race (P= 0.04).

CONCLUSION

Two polymorphisms within the IL-1 gene cluster are associated with ESRD independent of race. This finding is one of the strongest associations between genotype and ESRD reported, and suggests that polymorphisms in the IL-1 gene cluster affect the risk of development of ESRD.

RATIONALE

Repeated, short-term exposures to ozone (O3) lead to attenuation of the acute lung function and airway inflammatory responses seen after a single exposure in healthy subjects, but it is unclear whether these acute responses also attenuate in subjects with asthma.

OBJECTIVE

To address this question by exposing 14 subjects with asthma to 0.2 ppm O3 for either 4 hours on a single day or 4 hours on 4 consecutive days (multiday [MD]). At least 3 weeks later, subjects underwent the alternate exposure.

METHODS

Spirometry was performed immediately pre- and postexposure and bronchoalveolar lavage (BAL) was obtained 18 hours after each exposure.

MAIN RESULTS

The decrease in FEV1 was greatest across Day 2 of the MD (MD2) exposure and then gradually declined on successive days of the MD exposure (mean +/- SD decrease in FEV1 of 25.4 +/- 18.0% across MD2 compared with 4.2 +/- 6.5% across MD4). Respiratory symptoms followed a similar pattern to that of FEV1. Although the concentration of neutrophils in BAL after the MD4 exposure was not significantly different from that after the single-day exposure (1.7 +/- 1.3 x 10(4) cells/ml vs. 1.2 +/- 0.8 x 10(4) cells/ml, p = 0.20), the concentration of alveolar macrophages did significantly increase in BAL after the MD exposure (19.9 +/- 9.7 x 10(4) cells/ml after MD4 vs. 12.1 +/- 6.4 x 10(4) cells/ml after the single day).

CONCLUSIONS

Alveolar macrophages are recruited to the airways of subjects with asthma with repeated short-term exposures to O3, suggesting a possible role for these cells in the chronic response to oxidant-induced injury.

BACKGROUND

Little is known about the participation of minorities in health behavior research. This manuscript assesses factors associated with participation among women in four racial/ethnic groups.

METHODS

A total of 2800 Asian/Pacific Islander (API), Black, Latina, and non-Latina White women recruited through the San Francisco Mammography Registry was invited in 2002 and 2003 to participate in a telephone survey about breast cancer prevention.

RESULTS

Minorities participated at lower rates (49% for APIs, 60% for Latinas, and 64% for Blacks) than Whites (77%). Increased participation was associated with younger age for Latinas (OR = 1.90, 95% CI 1.05-3.44) and Whites (OR = 1.77, CI 1.08-2.91), and with a family history of breast cancer for APIs (OR = 2.09, CI 1.24-3.52). Decreased participation was associated with having less than a high school education for APIs (OR = 0.47, CI 0.26-0.86), Blacks (OR = 0.29, CI 0.11-0.78), and Latinas (OR = 0.51, CI 0.28-0.94).

CONCLUSIONS

Results suggest minorities' participation in health behavior research does not match Whites' and should be enhanced.

Using high-throughput screening, Jo et al. in this issue of Chemistry & Biology [1] have identified SEW2871 as a structurally unique sphingosine 1-phosphate(1) (S1P(1)) receptor agonist. SEW2871 binds to and activates the S1P(1) receptor and initiates a survival signaling pathway similar to that of S1P.