Dataset Information

Interaction of the GCKR and A1CF loci with alcohol consumption to influence the risk of gout.

ABSTRACT: Some gout-associated loci interact with dietary exposures to influence outcome. The aim of this study was to systematically investigate interactions between alcohol exposure and urate-associated loci in gout.A total of 2792 New Zealand European and Polynesian (M?ori or Pacific) people with or without gout were genotyped for 29 urate-associated genetic variants and tested for a departure from multiplicative interaction with alcohol exposure in the risk of gout. Publicly available data from 6892 European subjects were used to test for a departure from multiplicative interaction between specific loci and alcohol exposure for the risk of hyperuricemia (HU). Multivariate adjusted logistic and linear regression was done, including an interaction term.Interaction of any alcohol exposure with GCKR (rs780094) and A1CF (rs10821905) influenced the risk of gout in Europeans (interaction term 0.28, P?=?1.5?×?10-4; interaction term 0.29, P?=?1.4?×?10-4, respectively). At A1CF, alcohol exposure suppressed the gout risk conferred by the A-positive genotype. At GCKR, alcohol exposure eliminated the genetic effect on gout. In the Polynesian sample set, there was no experiment-wide evidence for interaction with alcohol in the risk of gout (all P?>?8.6?×?10-4). However, at GCKR, there was nominal evidence for an interaction in a direction consistent the European observation (interaction term 0.62, P?=?0.05). There was no evidence for an interaction of A1CF or GCKR with alcohol exposure in determining HU.These data support the hypothesis that alcohol influences the risk of gout via glucose and apolipoprotein metabolism. In the absence of alcohol exposure, genetic variants in the GCKR and A1CF genes have a stronger role in gout.

SUBMITTER: Rasheed H

PROVIDER: S-EPMC5499049 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Interaction of the GCKR and A1CF loci with alcohol consumption to influence the risk of gout.

Rasheed Humaira H Stamp Lisa K LK Dalbeth Nicola N Merriman Tony R TR

Arthritis research & therapy 20170705 1

<h4>Background</h4>Some gout-associated loci interact with dietary exposures to influence outcome. The aim of this study was to systematically investigate interactions between alcohol exposure and urate-associated loci in gout.<h4>Methods</h4>A total of 2792 New Zealand European and Polynesian (Māori or Pacific) people with or without gout were genotyped for 29 urate-associated genetic variants and tested for a departure from multiplicative interaction with alcohol exposure in the risk of gout. ...[more]

PMID: 28679452

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Project description: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.

Project description:ObjectiveTo explore the interaction effect between overweight/obesity and alcohol consumption on hypertension risk.DesignA longitudinal study of the independent and combined effects of hypertension risk factors.SettingTwelve provinces in China, including Beijing Liaoning, Heilongjiang, Shanghai, Jiangsu, Shandong, Henan, Hubei, Hunan, Guangxi, Guizhou and Chongqing.ParticipantsLongitudinal data of China Health and Nutrition Survey, collected between 2011 and 2015, were used in this study. A total of 13 121 residents from 12 provinces were included and completed physical examinations and questionnaires at baseline.OutcomeFirst incidence of hypertension.ResultsOver a mean follow-up of 4 years, 690 incident hypertension cases were reported. After adjusting for age, gender, education level, marital status, physical activity, diabetes and smoking, high body mass index (BMI) and light drinking (OR=5.07, 95% CI 3.06 to 8.41), high waist circumference (WC) and light drinking (OR=4.81, 95% CI 2.92 to 7.91), high waist hip ratio and light drinking (OR=2.85, 95% CI 1.84 to 4.42) were the highest risk of all participants in the three combinations. Multiplicative interaction measures were statistically significant in overweight/obesity and drinking/light drinking/heavy drinking categories in men (p<0.05). Additive interactions were observed between high BMI and drinking in men (relative excess risk due to interaction=1.75, 95% CI 0.85 to 2.65, attributable proportion due to interaction=0.56, 95% CI 0.36 to 0.76, synergy index=6.43, 95% CI 1.02 to 28.84).ConclusionsMeasures of body weight and size, particularly BMI and WC, appear to interact synergistically with alcohol consumption to increase the risk of hypertension in the Chinese population. Given that approximately 245 million people in China have hypertension, and that hypertension is a major cause of cardiovascular disease worldwide, our results may have implications for chronic disease prevention.

Dataset Information

Interaction of the GCKR and A1CF loci with alcohol consumption to influence the risk of gout.

Publications

Interaction of the GCKR and A1CF loci with alcohol consumption to influence the risk of gout.

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