Candidate genetic variants and antidepressant-related fall risk in middle-aged and older adults.

BACKGROUND: Antidepressant use has been associated with increased fall risk. Antidepressant-related adverse drug reactions (e.g. orthostatic hypotension) depend partly on genetic variation. We hypothesized that candidate genetic polymorphisms are associated with fall risk in older antidepressant users. METHODS: The association between antidepressant use and falls was cross-sectionally investigated in a cohort of Dutch older adults by logistic regression analyses. In case of significant interaction product term of antidepressant use and candidate polymorphism, the association between the variant genotype and fall risk was assessed within antidepressant users and the association between antidepressant use and fall risk was investigated stratified per genotype. Secondly, a look-up of the candidate genes was performed in an existing genome-wide association study on drug-related falls in antidepressant users within the UK Biobank. In antidepressant users, genetic associations for our candidate polymorphisms for fall history were investigated. RESULTS: In antidepressant users(n = 566), for rs28371725 (CYP2D6*41) fall risk was decreased in TC/variant allele carriers compared to CC/non-variant allele carriers (OR = 0.45, 95% CI 0.26-0.80). Concerning rs1057910 (CYP2C9*3), fall risk was increased in CA/variant allele carriers compared to AA/non-variant allele carriers (OR = 1.95, 95% CI 1.17-3.27). Regarding, rs1045642 (ABCB1), fall risk was increased in AG/variant allele carriers compared to GG/non-variant allele carriers (OR = 1.69, 95% CI 1.07-2.69). Concerning the ABCB1-haplotype (rs1045642/rs1128503), fall risk was increased in AA-AA/variant allele carriers compared to GG-GG/non-variant allele carriers (OR = 1.86, 95% CI 1.05-3.29). In the UK Biobank, in antidepressant users(n = 34,000) T/variant-allele of rs28371725 (CYP2D*41) was associated with increased fall risk (OR = 1.06, 95% CI 1.01-1.12). G/non-variant-allele of rs4244285 (CY2C19*2) was associated with decreased risk (OR = 0.96, 95% CI 0.92-1.00). CONCLUSION: This is the first study showing that certain genetic variants modify antidepressant-related fall risk. The results were not always consistent across the studies and should be validated in a study with a prospective design. However, pharmacogenetics might have value in antidepressant (de)prescribing in falls prevention.

[Epidemiological studies of blood levels of cholesterol and triglycerides in a school-age population of Veneto]. / Indagine epidemiologica sui livelli ematici del colesterolo e trigliceridi in una popolazione scolare del Venet.

During the school year 1974-75 serum cholesterol has been evaluated in the whole school population (520 subjects, 268 males and 252 females, age ranging from 6 to 14 years) of Saccolongo, a village which is about 20 kilometers from Padova (Italy) and serum triglycerides have been further evaluated in a random population of 161 subjects (90 males and 71 females, age ranging from 6 to 11 years). Serum cholesterol values did not show any significant difference between males and females. Analysis of serum cholesterol in the various age groups revealed that it was significantly higher in females at age 6 (t = 2.2296; p less than 0.05). A significant reduction in serum cholesterol values has been found at age 11 both in males (t = 4.7810; p less than 0.001) and in females (t = 5.6134; p less than 0.001). Serum cholesterol and triglycerides values did not correlate (r = 0.404). Serum triglycerides were higher in girls than in boys (t = 2.1360; p less than 0.05). Analysis of the serum triglycerides values in the various age groups were constant in males (F = 0.4161) and inconstant in females (F = 3.8844; p less than 0.01) where age groups 8 (t = 3.5127; p less than 0.005) and 11 (t = 3.5238; p less than 0.005) showed higher than normal values.