Publications

Preoperative breast pain in women with breast cancer may result from a number of causes. Previous work from our team found that breast pain occurred in 28.2% of women (n = 398) who were about to undergo breast cancer surgery. The occurrence of preoperative breast pain was associated with a number of demographic and clinical characteristics, as well as variation in two cytokine genes. Given that ion channels regulate excitability of sensory neurons, we hypothesized that variations in potassium channel genes would be associated with preoperative breast pain in these patients. Therefore, in this study, we evaluated for associations between single-nucleotide polymorphisms and inferred haplotypes among 10 potassium channel genes and the occurrence of preoperative breast pain in patients scheduled to undergo breast cancer surgery. Multivariable logistic regression analyses were used to identify those genetic variations that were associated with the occurrence of preoperative breast pain while controlling for age and genomic estimates of and self-reported race/ethnicity. Variations in four potassium channel genes: (1) potassium voltage-gated channel, delayed rectifier, subfamily S, member 1 (KCNS1); (2) potassium inwardly rectifying channel, subfamily J, member 3 (KCNJ3); (3) KCNJ6; and (4) potassium channel, subfamily K, member 9 (KCNK9) were associated with the occurrence of breast pain. Findings from this study warrant replication in an independent sample of women who report breast pain following one or more breast biopsies.

UNLABELLED

Hyperalgesic priming is a model of the transition from acute to chronic pain, in which previous activation of cell surface receptors or direct activation of protein kinase C epsilon markedly prolongs mechanical hyperalgesia induced by pronociceptive cytokines. We recently demonstrated a role of peripheral protein translation, alpha-calmodulin-dependent protein kinase II (αCaMKII) activation, and the ryanodine receptor in the induction of hyperalgesic priming. In the present study, we tested if they also mediate the prolonged phase of prostaglandin E2-induced hyperalgesia. We found that inhibition of αCaMKII and local protein translation eliminates the prolonged phase of prostaglandin E2 hyperalgesia. Although priming induced by receptor agonists or direct activation of protein kinase C epsilon occurs in male but not female rats, activation of αCaMKII and the ryanodine receptor also produces priming in females. As in males, the prolonged phase of prostaglandin E2-induced hyperalgesia in female rats is also protein kinase C epsilon-, αCaMKII-, and protein translation-dependent. In addition, in both male and female primed rats, the prolonged prostaglandin E2-induced hyperalgesia was significantly attenuated by inhibition of MEK/ERK. On the basis of these data, we suggest that the mechanisms previously shown to be involved in the induction of the neuroplastic state of hyperalgesic priming also mediate the prolongation of hyperalgesia.

PERSPECTIVES

The data provided by this study suggest that direct intervention on specific targets may help to alleviate the expression of chronic hyperalgesic conditions.

BACKGROUND

Asthma is a complex disease with both genetic and environmental causes. Genome-wide association studies of asthma have mostly involved European populations, and replication of positive associations has been inconsistent.

OBJECTIVE

We sought to identify asthma-associated genes in a large Latino population with genome-wide association analysis and admixture mapping.

METHODS

Latino children with asthma (n = 1893) and healthy control subjects (n = 1881) were recruited from 5 sites in the United States: Puerto Rico, New York, Chicago, Houston, and the San Francisco Bay Area. Subjects were genotyped on an Affymetrix World Array IV chip. We performed genome-wide association and admixture mapping to identify asthma-associated loci.

RESULTS

We identified a significant association between ancestry and asthma at 6p21 (lowest P value: rs2523924, P < 5 × 10(-6)). This association replicates in a meta-analysis of the EVE Asthma Consortium (P = .01). Fine mapping of the region in this study and the EVE Asthma Consortium suggests an association between PSORS1C1 and asthma. We confirmed the strong allelic association between SNPs in the 17q21 region and asthma in Latinos (IKZF3, lowest P value: rs90792, odds ratio, 0.67; 95% CI, 0.61-0.75; P = 6 × 10(-13)) and replicated associations in several genes that had previously been associated with asthma in genome-wide association studies.

CONCLUSIONS

Admixture mapping and genome-wide association are complementary techniques that provide evidence for multiple asthma-associated loci in Latinos. Admixture mapping identifies a novel locus on 6p21 that replicates in a meta-analysis of several Latino populations, whereas genome-wide association confirms the previously identified locus on 17q21.

OBJECTIVE

To monitor the effectiveness of the prevention of mother-to-child transmission (PMTCT) components in reducing mother-to-child transmission of HIV in Kilimanjaro region, Tanzania.

METHODS

We conducted a retrospective registry-based cohort study of HIV-exposed children aged 4 weeks to 18 months. Eligible children had a DNA polymerase chain reaction HIV antigen test between January 2009 and August 2012. We collected and analysed the data on the PMTCT components provided. We used logistic regression to explore factors associated with successful PMTCT usage and with infant infection.

RESULTS

We studied 561 children; 283 (50.5%) were from rural areas. Breastfeeding was reported by 519 (92.5%) of mothers. In 469 (83.6%) mother-baby pairs, both received chemoprophylaxis, whereas in 9 (1.6%) pairs, neither mother nor baby received any chemoprophylaxis. Of the 522 (93.0%) infants with known outcomes at 6 months, 227 (43.5%) were alive, 258 (49.4%) were lost to follow-up, 34 (6.5%) had transferred and 3 (0.6%) had died. A total of 54 (9.6%) children were infected. Transmission rates of HIV when only the mother (adjusted odds ratio [aOR] 1.49, 95% CI: 0.47-4.77) or only the baby (aOR 1.06, 95% CI: 0.23-5.01) received chemoprophylaxis were not significantly different from transmission rates when both mother and baby received antiretroviral chemoprophylaxis. Mixed feeding practices were not associated with significantly increased risk (aOR 4.09, 95% CI: 0.58-28.76) compared with exclusive breastfeeding.

CONCLUSION

This study showed that rate of MTCT of HIV was 9.6% in Tanzania between 2009 and 2012. The intrapartum and child chemoprophylaxis components of the PMTCT programme were well implemented with 84% of both mothers and their babies getting full chemoprophylaxis, and effective in reducing mother-to-child transmission.