Modifying Effect of N‐Acetyltransferase 2 Genotype on the Association Between Systemic Lupus Erythematosus and Consumption of Alcohol and Caffeine‐Rich Beverages

Abstract

Objective. N-acetyltransferase 2 (NAT2) is involved in the metabolism of various environmental substances, both with and without carcinogenic potential. Alcoholic and nonalcoholic caffeine-rich beverages may be associated with markers of inflammation. Systemic lupus erythematosus (SLE) is a chronic, multifaceted inflammatory disease. We investigated the effects of alcoholic and nonalcoholic caffeine-rich beverages on risk of SLE and determined whether the effects were modified by NAT2 status. Methods. The NAT2 polymorphism was genotyped in 152 SLE cases and 427 healthy controls, all women and Japanese. We assessed effect modification by testing an interaction term for the NAT2 polymorphism and consumption of beverages. Results. Consumption of black tea (odds ratio [OR] 1.88, 95% confidence interval [95% CI] 1.03-3.41) and coffee (OR 1.57, 95% CI 0.95-2.61), but not green tea, was associated with an increased risk of SLE, while alcohol use (OR 0.33, 95% CI 0.20 -0.55) was associated with a decreased risk of SLE. There were significant interactions between the NAT2 polymorphism and either alcohol use (P interaction ‫؍‬ 0.026) or consumption of black tea (P interaction ‫؍‬ 0.048). Conclusion. The NAT2 polymorphism significantly modified the effects of alcohol use and black tea consumption on SLE, emphasizing the importance of incorporating genetic and metabolic information in studies on management of SLE. Additional studies are warranted to confirm the findings suggested in this study.

Influence of Alcohol Consumption on the Risk of Systemic Lupus Erythematosus Among Women in the Nurses’ Health Study Cohorts

“…A study from Japan has reported an interaction between alcohol intake and N‐acetyltransferase 2 (NAT2) genotype (NAT2 rapid acetylators have a lower risk of SLE than do NAT2 slow acetylators) in SLE risk . This study suggests that the presence of a genotype associated with rapid acetylation (versus slow) and ever consuming alcohol (versus never) reduced SLE risk to an OR of 0.08 (95% CI 0.03–0.28) ( P interaction = 0.026).…”

Characterizing Blood Metabolomics Profiles Associated with Self-Reported Food Intakes in Female Twins

“…One of our top associations with coffee is 1-methylxanthine, a product of caffeine metabolism that was associated with a variant in NAT2 (rs4921914), liver NAT2 acetylates caffeine metabolites [ 61 ]. Recently a polymorphism in NAT2 has been found to modulate the association between black tea consumption and SLE risk [ 62 ].…”

Environmental exposures and the development of systemic lupus erythematosus

“…Women consuming >200 ml of coffee per day had increased inflammation markers, such as interleukin-6 and tumor necrosis factor-α, compared with coffee non-drinkers(137). A prior case-control study suggests a significant increased SLE risk with black tea consumption and borderline increased risk with coffee consumption, but not green tea(138). Previous data suggests that low intake of omega-3 and high intake of carbohydrate among patients with SLE are associated with increased disease activity (139).…”