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Biomedical subjects

David Strachan

Publications and source records attributed to David Strachan.

5 recordsLinked to original sources

Investigation of the MHC2TA gene, associated with rheumatoid arthritis in a Swedish population, in a UK rheumatoid arthritis cohort.

OBJECTIVE: A recent study of rheumatoid arthritis (RA) showed an association with a functional single-nucleotide polymorphism (SNP) mapping to the promoter region of the MHC2TA gene on chromosome 16p13 in a Swedish population. Interestingly, evidence for linkage to this region has been detected previously in a subgroup of UK RA families carrying 2 copies of shared epitope (SE) alleles. Therefore, we undertook this study to investigate the association of the MHC2TA gene promoter with RA in a UK Caucasian population. METHODS: Association with 5 SNPs spanning the promoter region of the MHC2TA gene was investigated in 813 UK RA patients and 532 population controls. Association with a functional putative RA-causal polymorphism (-168*G/A [rs3087456]) was tested in a total of 1,401 UK RA patients and 2,475 controls. Genotyping was performed using a Sequenom MassArray platform. Estimated haplotype frequencies were generated using the expectation-maximization algorithm and compared between patients and controls. RESULTS: All SNPs were in Hardy-Weinberg equilibrium. No evidence for association was found, either with the putative RA-causal polymorphism (-168*G/A) or with the other SNPs tested. Haplotype analysis revealed extensive linkage disequilibrium across the promoter region but no evidence for association. Stratifying the data set by carriage of SE alleles did not alter the conclusions. CONCLUSION: A functional polymorphism of the MHC2TA gene locus previously associated with RA in a European population has not been associated with RA in a UK population. These findings do not provide support for the notion that this gene plays a major role in the etiology of RA.

Adult↗

Control of exposure to mite allergen and allergen-impermeable bed covers for adults with asthma.

BACKGROUND: The effectiveness of avoidance of house-dust-mite allergen (Dermatophagoides pteronyssinus 1 [Der p1]) in the management of asthma is uncertain. METHODS: We conducted a double-blind, randomized, placebo-controlled study of allergen-impermeable bed covers involving 1122 adults with asthma. The primary outcomes were the mean morning peak expiratory flow rate over a four-week period during the run-in phase and at six months and the proportion of patients who discontinued inhaled corticosteroid therapy as part of a phased-reduction program during months 7 through 12. Der p1 was measured in mattress dust in a 10 percent random subsample of homes at entry and at 6 and 12 months. RESULTS: The prevalence of sensitivity to dust-mite allergen was 65.4 percent in the group supplied with allergen-impermeable bed covers (active-intervention group) and 65.1 percent in the control group supplied with non-impermeable bed covers. The concentration of Der p1 in mattress dust was significantly lower in the active-intervention group at 6 months (geometric mean, 0.58 microg per gram vs. 1.71 microg per gram in the control group; P=0.01) but not at 12 months (1.05 microg per gram vs. 1.64 microg per gram; P=0.74). The mean morning peak expiratory flow rate improved significantly in both groups (from 410.7 to 419.1 liters per minute in the active-intervention group, P<0.001 for the change; and from 417.8 to 427.4 liters per minute in the control group, P<0.001 for the change). After adjustment for base-line differences (by analysis of covariance), there was no significant difference between the groups in the peak expiratory flow rate at six months (difference in means, active-intervention group vs. control group, -1.6 liters per minute [95 percent confidence interval, -5.9 to 2.7] among all patients [P=0.46] and -1.5 liters per minute [95 percent confidence interval, -6.9 to 3.9] among mite-sensitive patients [P=0.59]). There was no significant difference between the groups in the proportion in whom complete cessation of inhaled corticosteroid therapy was achieved (17.4 percent in the active-intervention group and 17.1 percent in the control group) or in the mean reduction in steroid dose, either among all patients or among mite-sensitive patients. CONCLUSIONS: Allergen-impermeable covers, as a single intervention for the avoidance of exposure to dust-mite allergen, seem clinically ineffective in adults with asthma.

Adrenal Cortex Hormones↗

Reduced risk of atopy among school-age children infected with geohelminth parasites in a rural area of the tropics.

BACKGROUND: Childhood infections might protect against the expression of atopy. Geohelminths are among the most prevalent infections of childhood and might contribute to the low prevalence of allergic disease reported from rural areas of the tropics. OBJECTIVE: We sought to establish whether geohelminth infections protect against atopy and to explore whether this protection is dependent on infection chronicity. METHODS: The risk of atopy (measured by means of allergen skin test reactivity) associated with active geohelminth infections (measured by means of the presence of eggs in stool samples) or with chronic geohelminth infections (measured by means of high levels [>/=3564 IU/mL] of total serum IgE or the presence of detectable anti-Ascaris lumbricoides IgG4 antibodies) was investigated in an analytic cross-sectional study conducted among school-age children attending rural schools in Pichincha Province in Ecuador. RESULTS: A total of 2865 children aged 5 to 19 years from 55 schools was examined. Active infection with any geohelminth and infections with A lumbricoides or Ancylostoma duodenale were associated with significant protective effects against allergen skin test reactivity. Children with the highest levels of total IgE or with anti-A lumbricoides IgG4 antibodies were protected against skin test reactivity also, and the protective effects of high IgE or anti-A lumbricoides IgG4 and or active geohelminth infections were statistically independent. CONCLUSION: Active infections with geohelminth parasites and the presence of serologic markers of chronic infections (high levels of total serum IgE or anti-A lumbricoides IgG4) are independent protective factors against allergen skin test reactivity among school-age children living in an endemic region of the rural tropics.

Adolescent↗

Lung function and cognitive ability in a longitudinal birth cohort study.

OBJECTIVE: The objective of this study was to examine the association between forced expiratory volume in 1 second (FEV1) and cognitive ability in midlife in the normal population. METHODS: Multiple regression was used to test associations between FEV1 and cognitive function in 1778 men and women in the MRC National Survey of Health and Development, also known as the British 1946 birth cohort. Analyses were adjusted for sex, body size (birth weight, adult height, weight, and chest circumference), socioeconomic status, lifetime smoking, and a range of health indicators, including early respiratory vulnerability (infant lower respiratory infection, childhood asthma, and exposure to atmospheric pollution). RESULTS: FEV1 at 43 years was associated with slower psychomotor speed (peg placement) at the same age and with slower decline in psychomotor speed (letter search speed) from 43 to 53 years, independently of the previously mentioned potential confounders. These independent associations were not observed, however, for adult verbal ability, verbal memory, or rate of decline in memory, which were significantly explained by socioeconomic status and adolescent cognitive ability. In a subsequent analysis, adolescent cognition was positively associated with FEV1, although not with rate of decline in FEV1 from 43 to 53 years, again independently of the previously mentioned confounders. CONCLUSIONS: Cognitive function and FEV1 are positively associated across the life course. One possible explanation lies in the parallel action of endocrine, autonomic, and motor control systems on respiration and higher mental function. Because respiration and mental function are both associated with functional capacity and survival, this is a matter of potential clinical significance.

Adolescent↗