E Dennison

Effect of five genetic variants associated with lung function on the risk of chronic obstructive lung disease, and their joint effects on lung function

RATIONALEnGenomic loci are associated with FEV1 or the ratio of FEV1 to FVC in population samples, but their association with chronic obstructive pulmonary disease (COPD) has not yet been proven, nor have their combined effects on lung function and COPD been studied.nnnOBJECTIVESnTo test association with COPD of variants at five loci (TNS1, GSTCD, HTR4, AGER, and THSD4) and to evaluate joint effects on lung function and COPD of these single-nucleotide polymorphisms (SNPs), and variants at the previously reported locus near HHIP.nnnMETHODSnBy sampling from 12 population-based studies (n = 31,422), we obtained genotype data on 3,284 COPD case subjects and 17,538 control subjects for sentinel SNPs in TNS1, GSTCD, HTR4, AGER, and THSD4. In 24,648 individuals (including 2,890 COPD case subjects and 13,862 control subjects), we additionally obtained genotypes for rs12504628 near HHIP. Each allele associated with lung function decline at these six SNPs contributed to a risk score. We studied the association of the risk score to lung function and COPD.nnnMEASUREMENTS AND MAIN RESULTSnAssociation with COPD was significant for three loci (TNS1, GSTCD, and HTR4) and the previously reported HHIP locus, and suggestive and directionally consistent for AGER and TSHD4. Compared with the baseline group (7 risk alleles), carrying 10-12 risk alleles was associated with a reduction in FEV1 (β = -72.21 ml, P = 3.90 × 10(-4)) and FEV1/FVC (β = -1.53%, P = 6.35 × 10(-6)), and with COPD (odds ratio = 1.63, P = 1.46 × 10(-5)).nnnCONCLUSIONSnVariants in TNS1, GSTCD, and HTR4 are associated with COPD. Our highest risk score category was associated with a 1.6-fold higher COPD risk than the population average score.

The relationship of dietary patterns with adult lung function and COPD

Previous studies of diet and lung function have focused on associations with individual nutrients and foods, and not dietary patterns. The relationships between dietary patterns and lung function and spirometrically defined chronic obstructive pulmonary disease (COPD) were investigated in 1,551 males and 1,391 females in Hertfordshire, UK. Dietary information was obtained by food frequency questionnaire and dietary patterns were identified using principal components analysis. Using regression analysis, after controlling for confounders, a “prudent” pattern (high consumption of fruit, vegetables, oily fish and wholemeal cereals) was positively associated with forced expiratory volume in 1 s (FEV1) (trend p-value <0.001 in males, 0.008 in females) (difference in FEV1 between top and bottom quintiles of pattern score, 0.18 L (95% CI 0.08–0.28 L) in males, 0.08 L (95% CI 0.00–0.16 L) in females). This pattern was also positively associated with forced vital capacity (FVC) in both sexes. Males with a higher “prudent” pattern score had a higher FEV1/FVC (trend p-value 0.002) and a lower prevalence of COPD (odds ratio comparing top versus bottom quintile 0.46, 95% CI 0.26–0.81; trend p-value 0.012). Associations in males were stronger in smokers than nonsmokers (interaction p-value for FEV1/FVC 0.002). A “prudent” dietary pattern may protect against impaired lung function and COPD, especially in male smokers.

The Epidemiology of Fractures

Fractures are a major cause of morbidity and mortality throughout the life course but particularly in the elderly. This article focuses on the epidemiology of fragility fractures that include hip, vertebral, forearm, and other fractures caused due to defects in bone strength. The cost of fragility fractures is large in terms of not only the health of individuals but also the cost to health-care systems, with hip fractures alone estimated to cost in excess of

Effect of five genetic variants associated with lung function on the risk of chronic obstructive lung disease, and their joint effects on lung function.

130 billion worldwide. The rate of fracture according to sex fluctuates throughout the life course with fractures in females being more common overall but more common in younger males than females due to more forceful, physical trauma. We will cover the epidemiology of hip, vertebral, and distal forearm fractures, as well as pediatric fractures; clustering of fractures; financial implications; and future directions of interest in this complex and important area of research.

The intrauterine programming of osteoporosis

RATIONALEnGenomic loci are associated with FEV1 or the ratio of FEV1 to FVC in population samples, but their association with chronic obstructive pulmonary disease (COPD) has not yet been proven, nor have their combined effects on lung function and COPD been studied.nnnOBJECTIVESnTo test association with COPD of variants at five loci (TNS1, GSTCD, HTR4, AGER, and THSD4) and to evaluate joint effects on lung function and COPD of these single-nucleotide polymorphisms (SNPs), and variants at the previously reported locus near HHIP.nnnMETHODSnBy sampling from 12 population-based studies (n = 31,422), we obtained genotype data on 3,284 COPD case subjects and 17,538 control subjects for sentinel SNPs in TNS1, GSTCD, HTR4, AGER, and THSD4. In 24,648 individuals (including 2,890 COPD case subjects and 13,862 control subjects), we additionally obtained genotypes for rs12504628 near HHIP. Each allele associated with lung function decline at these six SNPs contributed to a risk score. We studied the association of the risk score to lung function and COPD.nnnMEASUREMENTS AND MAIN RESULTSnAssociation with COPD was significant for three loci (TNS1, GSTCD, and HTR4) and the previously reported HHIP locus, and suggestive and directionally consistent for AGER and TSHD4. Compared with the baseline group (7 risk alleles), carrying 10-12 risk alleles was associated with a reduction in FEV1 (β = -72.21 ml, P = 3.90 × 10(-4)) and FEV1/FVC (β = -1.53%, P = 6.35 × 10(-6)), and with COPD (odds ratio = 1.63, P = 1.46 × 10(-5)).nnnCONCLUSIONSnVariants in TNS1, GSTCD, and HTR4 are associated with COPD. Our highest risk score category was associated with a 1.6-fold higher COPD risk than the population average score.

THE RELATIONSHIP BETWEEN INTRAUTERINE GROWTH AND POSTNATAL SKELETAL DEVELOPMENT

Osteoporosis is a skeletal disorder characterized by low bone mass and microarchitectural deterioration of bone tissue with a consequent increase in the risk of fracture. These fractures typically occur at the hip, spine, and distal forearm; the annual cost attributable to them in England and Wales is £1.7 billion, with over 90% of this figure ascribed to hip fracture [1]. Figure 1 shows the history of advances in the field of osteoporosis over the previous three millennia. The recognition that fractures might be a consequence of bone fragility was initiated in the writings of Hippocrates; palaeopathological studies of bone specimens removed from burial sites dating as early at the 8th century AD confirm that osteoporotic vertebral collapse has occurred among elderly individuals throughout the ages. Our recent enhanced understanding of the disorder, however, stems from the work of orthopedic surgeons such as Sir Astley Cooper in 1825, who documented the descriptive characteristics of age-related fractures, and the observations of histopathologists in France and Germany at around the same time, who first coined the time “osteoporosis” to denote the rarification of trabecular architecture observed in the central part of vertebral bodies from patients who were elderly, when compared with those who had died at younger ages. The modern era of osteoporosis research originated in the research of Dr. Albright in the United States, who first documented osteoporotic vertebral deformity as a consequence of estrogen deficiency in postmenopausal women.