Association between loss-of-function mutations in the filaggrin gene and self-reported food allergy and alcohol sensitivity.

BACKGROUND: Loss-of-function mutations of the filaggrin (FLG) gene cause an impaired skin barrier and increase the risk of atopic dermatitis. Interestingly, FLG mutations have also been found to be associated with a high risk of peanut allergy. OBJECTIVE: We investigated the association of FLG mutations with self-reported food allergy, symptoms of oral allergy syndrome (OAS), and alcohol sensitivity. METHODS: A total of 3,471 adults from the general population participated in a health examination. Information on food allergies, OAS and alcohol sensitivity was obtained by questionnaire. FLG mutation carriers were defined as having at least one null mutation allele of R501X or 2282del4. Primary lactose intolerance (PLI) was defined as the C/C genotype of the rs4988235 polymorphism. RESULTS: FLG mutations were associated with a higher risk of self-reported allergy to eggs (OR 3.22 and 95% CI 1.46-7.11), milk (OR 2.10 and 95% CI 1.12-3.92), fish (OR 4.54 and 95% CI 1.88-10.96) and wheat (OR 3.59 and 95% CI 1.61-8.02), but not with symptoms of OAS (OR 1.05 and 95% CI 0.73-1.51). Serum-specific IgE was measured in a subsample and confirmed the association between FLG and IgE to milk. A significant gene-by-gene interaction between FLG and PLI was observed in relation to self-reported allergy to milk. Furthermore, FLG mutations were associated with a higher risk of alcohol sensitivity. CONCLUSIONS: We found that loss-of-function mutations in the FLG gene were significantly associated with self-reported food allergy and alcohol sensitivity, but not with OAS. These findings, if confirmed, support the idea that skin barrier functions may be involved in the pathogenesis of food allergy.

Fibrillin-1 genotype and risk of prevalent hypertension: a study in two independent populations.

OBJECTIVE: Mutations in the fibrillin-1 gene are the cause of Marfan syndrome. We wanted to investigate the relationship between a mutation in this gene and risk of prevalent hypertension. METHODS: In a cross-sectional study, the effect of a G-A substitution in intron 27 in the fibrillin-1 gene (rs11856553) on risk of prevalent hypertension was studied in two large population-based studies: the Health 2006 study, consisting of 3193 women and men, age 18-69 years, and the MONICA10 study, consisting of 2408 women and men, age 41-72 years. In 1646 MONICA10 participants, blood pressure (BP) was also measured by 24-h ambulatory recordings. RESULTS: Among the 3193 Health 2006 participants 23 had the G-A variant, and among the 2408 MONICA10 participants 18 had the G-A variant. In Health 2006, the odds ratio estimate (95% confidence intervals) for the G-A variant for risk of hypertension, defined as systolic (S) BP ≥ 140 mmHg or diastolic (D) BP ≥ 90 mmHg or on antihypertensive medicine, was 2.67 (1.14-6.18), p = 0.022. The corresponding figure for moderate to severe hypertension, defined as SBP ≥ 160 mmHg or DBP ≥ 100 mmHg, was 9.68 (4.24-22.12), p < 0.0001. In MONICA10, the odds ratio estimate (95% confidence intervals) for the G-A variant for risk of moderate to severe ambulatory hypertension, defined as 24-h mean SBP ≥ 150 mmHg or 24-h mean DBP ≥ 90 mmHg, was 5.73 (1.96-16.7), p = 0.0014. CONCLUSION: The G-A substitution in the fibrillin-1 gene (rs11856553) is a rare genetic variant that is associated with an increased risk of prevalent hypertension, particularly of moderate to severe prevalent hypertension.

Genetic variation in the natriuretic peptide system, circulating natriuretic peptide levels, and blood pressure: an ambulatory blood pressure study.

BACKGROUND: In a large collaborative study (n > 50,000), common variants in the natriuretic peptide (NP) genes were found to be associated with circulating NP levels and also with blood pressure (BP) levels based on office BP measurements (OBPMs). It is unknown if determining an individual's BP by 24-h ambulatory BP measurements (ABPMs) will influence the effect of NP gene variations on BP levels. METHODS: We used rs632793 at the NPPB (NP precursor B) locus to investigate the relationship between genetically determined serum N-terminal pro-brain NP (NT-proBNP) concentrations and BP levels determined by both 24-h ABPMs and OBPMs in a population consisting of 1,397 generally healthy individuals taking no BP-lowering drugs. RESULTS: rs632793 was significantly correlated with serum Nt-proBNP levels (r = 0.10, P = 0.0003), and participants with the A:A genotype had lower serum Nt-proBNP levels than participants with the G:G genotype (geometric mean (95% confidence interval (CI)): 34.8 (31.5-38.4) pg/ml vs. 48.1 (41.9-55.3) pg/ml, P = 0.0002), but higher 24-h ambulatory BP levels (mean difference (95% CI): 2.0 (0.1-4.1) mm Hg, P = 0.043, for systolic BP and 1.7 (0.4-3.1) mm Hg, P = 0.011, for diastolic BP). Office BP decreased across the genotypes from A:A to G:G, but the differences did not reach statistical significance (P ≥ 0.12). CONCLUSIONS: This study suggests that 24-h ABPMs is a better method than OBPMs to detect significant differences in BP levels related to genetic variance and provides further evidence that the NP system plays an important role in BP regulation.