A comprehensive analysis of the COL29A1 gene does not support a role in eczema.

BACKGROUND: Based on a recent positional cloning approach, it was claimed that the collagen 29A1 gene (COL29A1), which encodes an epidermal collagen, represents a major risk gene for eczema underlying a previously reported linkage to chromosome 3q21. However, thus far, not a single replication attempt has been published, and no definitive functional data have been provided. OBJECTIVES: We aimed to determine whether COL29A1 polymorphisms contribute to eczema susceptibility and whether COL29A1 expression is altered in eczema. METHODS: We investigated the reported association of COL29A1 variants with eczema, subtypes of eczema, and eczema-related traits in 5 independent and large study populations comprehensively phenotyped for allergic diseases: a set of 1687 German patients with eczema and 2387 population control subjects, a collection of 274 German families with eczema-diseases children, a cross-sectional population of German children (n = 3099), the Swedish population-based birth cohort Children Allergy and Milieu in Stockholm, an Epidemiologic Study (BAMSE) (n = 2033), and the European cross-sectional Prevention of Allergy-Risk Factors for Sensitization Related to Farming and Anthroposophic Lifestyle (PARSIFAL) study (n = 3113). An additional set of 19 COL29A1 coding single nucleotide polymorphisms was analyzed in BAMSE and PARSIFAL. COL29A1 expression was investigated by using in situ hybridization. RESULTS: We found no evidence for a relationship between COL29A1 polymorphisms and eczema. The equivalence test rejected the hypothesis of association even excluding small effects. In situ hybridization carried out on biopsy specimens from lesional and nonlesional skin of patients with eczema and from healthy control subjects did not show any differences in the cellular distribution pattern of COL29A1 expression at the mRNA level. CONCLUSIONS: Our results suggest that COL29A1 is unlikely to contain genetic variants that have a major effect on eczema or atopy susceptibility.

Analysis of the individual and aggregate genetic contributions of previously identified serine peptidase inhibitor Kazal type 5 (SPINK5), kallikrein-related peptidase 7 (KLK7), and filaggrin (FLG) polymorphisms to eczema risk.

BACKGROUND: Polymorphisms in the serine protease inhibitor gene serine peptidase inhibitor Kazal type 5 (SPINK5) and the serine protease kallikrein-related peptidase 7 gene (KLK7) appear to confer risk to eczema in some cohorts, but these findings have not been widely replicated. These genes encode proteins thought to be involved in the regulation of posttranslation processing of filaggrin (FLG), the strongest identified genetic risk factor for eczema to date. OBJECTIVES: We sought to clarify the individual risk of eczema conferred by the SPINK5 polymorphism rs2303067 (Glu420Lys) and a previously described insertion in the 3' untranslated region of KLK7 and to examine potential epistatic effects between these variants and FLG mutations. METHODS: Initially, we examined the effects of these polymorphisms and FLG in 486 unrelated patients from a German family-based study, an additional 287 German patients, and 418 unrelated Irish/English patients with eczema (n for 3 genes studied = 1191 vs 4544 control subjects). We then additionally studied the SPINK5 polymorphism and FLG mutations in 1583 patients with eczema from the Avon Longitudinal Study of Parents and Children cohort (sample size for 2 genes studied = 2774 vs 10,607 control subjects). RESULTS: No association was seen with the SPINK5 or KLK7 variants in the case-control analysis; however, a weaker effect was observed for the SPINK5 variant with maternal transmission in the family-based study. No interactions were seen between the polymorphisms in KLK7, SPINK5, and FLG. CONCLUSION: The SPINK5 420LysSer mutation confers a risk of eczema when maternally inherited but is not a major eczema risk factor. The KLK7 insertion appears to confer no risk of eczema. We found no interaction between the SPINK5 risk allele or the putative KLK7 risk allele and FLG mutations.

Decline of FEV1 in scuba divers.

STUDY OBJECTIVES: Obstructive changes in lung function have been reported with cumulative scuba diving exposure. The aim of this study was to investigate the decline in FEV1 in scuba divers over time. DESIGN: Prospective controlled cohort study. SETTING: German Naval Medical Institute. PATIENTS: Four hundred sixty-eight healthy, male, military scuba divers and 122 submariners (control subjects) were entered. MEASUREMENTS AND RESULTS: Pulmonary function tests were performed in all subjects on at least three occasions with a minimum interval of 1 year between first and last measurement. The decline in FEV1 was investigated fitting a general linear model to FEV1 across time with a factorial main-effects model for slopes and intercepts with respect to the factors group, smoking status, and baseline FEV1. Mean baseline age of all subjects was 32 years (SD, 9.1), and mean body mass index was 24.7 kg/m2 (SD, 2.4). Subjects were followed up for 5 years (range, 1 to 9 years) on average. Baseline FEV1 exceeded the predicted values in both divers and nondiving control subjects. There was no significant difference in the decline of FEV1 between divers and control subjects. Over time, FEV1 declined more rapidly in smokers than in nonsmokers (p = 0.0064) and declined more rapidly also in subjects with a baseline FEV1 above average compared to subjects below average (p < 0.0001). The annual decline of FEV1 peaked in smoking divers who had a high FEV1 at baseline. CONCLUSIONS: The data indicate that scuba diving is not associated with an accelerated decline in FEV1. Combined exposure to diving and smoking contributes to the fall of FEV1; therefore, smoking cessation is advised for divers.