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Association of the lipoprotein receptor-related protein 2 gene with gout and non-additive interaction with alcohol consumption.

ABSTRACT: The T allele of a single nucleotide polymorphism (SNP: rs2544390) in lipoprotein receptor-related protein 2 (LRP2) is associated with higher serum urate and risk of gout in Japanese individuals. SNP rs2544390 also interacts with alcohol consumption in determining hyperuricemia in this population. We investigated the association of rs2544390 with gout, and interaction with all types of alcohol consumption in European and New Zealand (NZ) M?ori and Pacific subjects, and a M?ori study cohort from the East Coast region of NZ's North Island.Rs2544390 was genotyped by Taqman®. From NZ a total of 1205 controls and 1431 gout cases clinically ascertained were used. Publicly available genotype and serum urate data were utilized from the Atherosclerosis Risk in Communities (ARIC) study and the Framingham Heart Study (FHS). Alcohol consumption data were obtained by consumption frequency questions in all study cohorts. Multivariate adjusted logistic regression was done using STATA.The T allele of rs2544390 was associated with increased risk of gout in the combined M?ori and Pacific Island cohort (OR?=?1.20, P?=?0.009), and associated with gout in the European subjects, but with a protective effect (OR?=?0.79, PUnadjusted?=?0.02). Alcohol consumption was positively associated with risk of gout in M?ori and Pacific subjects (0.2% increased risk/g/week, P?=?0.004). There was a non-additive interaction between any alcohol intake and the risk of gout in the combined M?ori and Pacific cohorts (PInteraction?=?0.001), where any alcohol intake was associated with a 4.18-fold increased risk in the CC genotype group (P?=?6.6x10-5), compared with a 1.14-fold increased risk in the CT/TT genotype group (P?=?0.40). These effects were not observed in European subjects.Association of the T-allele with gout risk in the M?ori and Pacific subjects was consistent with this allele increasing serum urate in Japanese individuals. The non-additive interaction in the M?ori and Pacific subjects showed that alcohol consumption over-rides any protective effect conferred by the CC genotype. Further exploration of the mechanism underlying this interaction should generate new understanding of the biological role of alcohol in gout, in addition to strengthening the evidence base for reduction of alcohol consumption in the management of gout.

SUBMITTER: Rasheed H

PROVIDER: S-EPMC3979038 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Association of the lipoprotein receptor-related protein 2 gene with gout and non-additive interaction with alcohol consumption.

Rasheed Humaira H Phipps-Green Amanda A Topless Ruth R Hollis-Moffatt Jade E JE Hindmarsh Jennie Harré JH Franklin Christopher C Dalbeth Nicola N Jones Peter B PB White Douglas H N DH Stamp Lisa K LK Merriman Tony R TR

Arthritis research & therapy 20131104 6

<h4>Introduction</h4>The T allele of a single nucleotide polymorphism (SNP: rs2544390) in lipoprotein receptor-related protein 2 (LRP2) is associated with higher serum urate and risk of gout in Japanese individuals. SNP rs2544390 also interacts with alcohol consumption in determining hyperuricemia in this population. We investigated the association of rs2544390 with gout, and interaction with all types of alcohol consumption in European and New Zealand (NZ) Māori and Pacific subjects, and a Māor ...[more]

PMID: 24286387

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Project description:Despite the pervasive use of social media by young adults, there is comparatively little known about whether, and how, engagement in social media influences this group's drinking patterns and risk of alcohol-related problems. We examined the relations between young adults' alcohol-related social media engagement (defined as the posting, liking, commenting, and viewing of alcohol-related social media content) and their drinking behavior and problems. We conducted a systematic review and meta-analysis of studies evaluating the association of alcohol consumption and alcohol-related problems with alcohol-related social media engagement. Summary baseline variables regarding the social media platform used (e.g., Facebook and Twitter), social media measures assessed (e.g., number of alcohol photographs posted), alcohol measures (e.g., Alcohol Use Disorders Identification Test and Timeline Follow back Interview), and the number of time points at which data were collected were extracted from each published study. We used the Q statistic to examine heterogeneity in the correlations between alcohol-related social media engagement and both drinking behavior and alcohol-related problems. Because there was significant heterogeneity, we used a random-effects model to evaluate the difference from zero of the weighted aggregate correlations. We used metaregression with study characteristics as moderators to test for moderators of the observed heterogeneity. Following screening, 19 articles met inclusion criteria for the meta-analysis. The primary findings indicated a statistically significant relationship and moderate effect sizes between alcohol-related social media engagement and both alcohol consumption (r = 0.36, 95% CI: 0.29 to 0.44, p < 0.001) and alcohol-related problems (r = 0.37, 95% CI: 0.21 to 0.51, p < 0.001). There was significant heterogeneity among studies. Two significant predictors of heterogeneity were (i) whether there was joint measurement of alcohol-related social media engagement and drinking behavior or these were measured on different occasions and (ii) whether measurements were taken by self-report or observation of social media engagement. We found moderate-sized effects across the 19 studies: Greater alcohol-related social media engagement was correlated with both greater self-reported drinking and alcohol-related problems. Further research to determine the causal direction of these associations could provide opportunities for social media-based interventions with young drinkers aimed at reducing alcohol consumption and alcohol-related adverse consequences.

Project description:OBJECTIVE:Light to moderate alcohol consumption has been widely established to be protective against coronary heart disease (CHD), whereas heavy alcohol consumption has been shown to have a potential detrimental effect. The reduction in risk of CHD associated with light and moderate alcohol intake is generally attributed to the beneficial effects of alcohol on high-density lipoprotein (HDL) cholesterol levels. Previous research in the Atherosclerosis Risk in Communities (ARIC) study showed all levels of alcohol consumption to be protective against CHD in whites but to be associated with an increased risk of CHD in black men. We investigated the ARIC cohort to determine whether risk of incident CHD is influenced by an interaction effect between alcohol intake and genetic variation involved in the regulation of HDL cholesterol. Genes of interest included cholesterol ester transfer protein (CETP), lipoprotein lipase (LPL), hepatic lipase (HL), and paraoxonase-1 (PON1). METHOD:Participants were selected from the ARIC study, a prospective investigation of atherosclerosis and its clinical sequelae, involving 15,792 individuals, ages 45-64 years at recruitment (1987-1989). Incident CHD was identified through annual telephone calls and hospital and death certificate surveillance. Because of ethnic differences in the alcohol-CHD relationship observed in the ARIC cohort and pattern of alcohol consumption differences, statistical analyses were evaluated separately for each race-gender stratum (white men/women, black men/women). RESULTS:Genotype modified the relationship between heavy drinking and CHD risk but did not modify this relationship for light or moderate drinking. Interaction analyses were significant for heavy alcohol intake and PON1 genotype (p=.02) in black men, with a suggested interaction for heavy alcohol intake and CETP genotype (p=.06) in black men. Heavy drinking was associated with an increased risk for CHD in black men with the PON1 QQ and CETP GG genotypes (PON1 hazard rate ratio [HRR]=17.3, 95% confidence interval [CI]: 1.76-170.2; CETP HRR=2.23, 95% CI: 1.01-4.91). CONCLUSIONS:Results from the current study suggest that interaction effects between alcohol consumption and HDL cholesterol metabolism gene variation influence the risk of incident CHD in black men. Additional studies are warranted to confirm these findings.

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Association of the lipoprotein receptor-related protein 2 gene with gout and non-additive interaction with alcohol consumption.

Publications

Association of the lipoprotein receptor-related protein 2 gene with gout and non-additive interaction with alcohol consumption.

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