Millwood_2016_Int.J.Epidemiol_45_1588

Reference

Title : A phenome-wide association study of a lipoprotein-associated phospholipase A2 loss-of-function variant in 90 000 Chinese adults - Millwood_2016_Int.J.Epidemiol_45_1588
Author(s) : Millwood IY , Bennett DA , Walters RG , Clarke R , Waterworth D , Johnson T , Chen Y , Yang L , Guo Y , Bian Z , Hacker A , Yeo A , Parish S , Hill MR , Chissoe S , Peto R , Cardon L , Collins R , Li L , Chen Z
Ref : Int J Epidemiol , 45 :1588 , 2016
Abstract : BACKGROUND: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) has been implicated in development of atherosclerosis; however, recent randomized trials of Lp-PLA(2) inhibition reported no beneficial effects on vascular diseases. In East Asians, a loss-of-function variant in the PLA2G7 gene can be used to assess the effects of genetically determined lower Lp-PLA(2) METHODS: PLA2G7 V279F (rs76863441) was genotyped in 91 428 individuals randomly selected from the China Kadoorie Biobank of 0.5 M participants recruited in 2004-08 from 10 regions of China, with 7 years' follow-up. Linear regression was used to assess effects of V279F on baseline traits. Logistic regression was conducted for a range of vascular and non-vascular diseases, including 41 ICD-10 coded disease categories. RESULTS: PLA2G7 V279F frequency was 5% overall (range 3-7% by region), and 9691 (11%) participants had at least one loss-of-function variant. V279F was not associated with baseline blood pressure, adiposity, blood glucose or lung function. V279F was not associated with major vascular events [7141 events; odds ratio (OR) = 0.98 per F variant, 95% confidence interval (CI) 0.90-1.06] or other vascular outcomes, including major coronary events (922 events; 0.96, 0.79-1.18) and stroke (5967 events; 1.00, 0.92-1.09). Individuals with V279F had lower risks of diabetes (7031 events; 0.91, 0.84-0.98) and asthma (182 events; 0.53, 0.28-0.98), but there was no association after adjustment for multiple testing. CONCLUSIONS: Lifelong lower Lp-PLA(2) activity was not associated with major risks of vascular or non-vascular diseases in Chinese adults. Using functional genetic variants in large-scale prospective studies with linkage to a range of health outcomes is a valuable approach to inform drug development and repositioning.
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PubMedID: 27301456
Gene_locus related to this paper: human-PLA2G7

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Gene_locus related to this paper: human-PLA2G7

Citations formats

Millwood IY, Bennett DA, Walters RG, Clarke R, Waterworth D, Johnson T, Chen Y, Yang L, Guo Y, Bian Z, Hacker A, Yeo A, Parish S, Hill MR, Chissoe S, Peto R, Cardon L, Collins R, Li L, Chen Z (2016)
A phenome-wide association study of a lipoprotein-associated phospholipase A2 loss-of-function variant in 90 000 Chinese adults
Int J Epidemiol 45 :1588

Millwood IY, Bennett DA, Walters RG, Clarke R, Waterworth D, Johnson T, Chen Y, Yang L, Guo Y, Bian Z, Hacker A, Yeo A, Parish S, Hill MR, Chissoe S, Peto R, Cardon L, Collins R, Li L, Chen Z (2016)
Int J Epidemiol 45 :1588