Lack of gene–diuretic interactions on the risk of incident gout: the Nurses’ Health Study and Health Professionals Follow-up Study

BackgroundDiuretic-induced gout might occur only among those with a genetic predisposition to hyperuricaemia, as suggested by a recent study with 108 self-reported gout cases.MethodsWe examined the role of urate genes on the risk of diuretic-induced incident gout in 6850 women from the Nurses’ Health Study (NHS) and in 4223 men from the Health Professionals Follow-up Study (HPFS). Two published genetic risk scores (GRSs) were calculated using urate-associated single-nucleotide polymorphisms for 8 (GRS8) and 29 genes (GRS29).ResultsOur analyses included 727 and 354 confirmed incident gout cases in HPFS and NHS, respectively. The multivariate relative risk (RR) for diuretic use was 2.20 and 1.69 among those with GRS8 < and ≥ the median (p for interaction=0.27). The corresponding RRs using GRS29 were 2.19 and 1.88 (p for interaction=0.40). The lack of interaction persisted in NHS (all p values >0.20) and in our analyses limited to those with hypertension in both cohorts. SLC22A11 (OAT4) showed a significant interaction only among women but in the opposite direction to the recent study.ConclusionsIn these large prospective studies, individuals with a genetic predisposition for hyperuricaemia are not at a higher risk of developing diuretic-induced gout than those without.

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Impact of adiposity on risk of female gout among those genetically predisposed: sex-specific prospective cohort study findings over >32 years

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-221635 ◽

2021 ◽

pp. annrheumdis-2021-221635

Author(s):

Natalie McCormick ◽

Chio Yokose ◽

Na Lu ◽

Amit D Joshi ◽

Gary C Curhan ◽

...

Keyword(s):

Genetic Predisposition ◽

Genetic Risk Score ◽

Joint Effect ◽

Health Study ◽

Nucleotide Polymorphisms ◽

Additive Interaction ◽

Individual Factor ◽

Single Nucleotide ◽

Excess Adiposity

ObjectivesTo evaluate the joint (combined) association of excess adiposity and genetic predisposition with the risk of incident female gout, and compare to their male counterparts; and determine the proportion attributable to body mass index (BMI) only, genetic risk score (GRS) only, and to their interaction.MethodsWe prospectively investigated potential gene-BMI interactions in 18 244 women from the Nurses’ Health Study and compared with 10 888 men from the Health Professionals Follow-Up Study. GRS for hyperuricaemia was derived from 114 common urate-associated single nucleotide polymorphisms.ResultsMultivariable relative risk (RR) for female gout was 1.49 (95% CI 1.42 to 1.56) per 5 kg/m2 increment of BMI and 1.43 (1.35 to 1.52) per SD increment in the GRS. For their joint association of BMI and GRS, RR was 2.18 (2.03 to 2.36), more than the sum of each individual factor, indicating significant interaction on an additive scale (p for interaction <0.001). The attributable proportions of joint effect for female gout were 42% (37% to 46%) to adiposity, 37% (32% to 42%) to genetic predisposition and 22% (16% to 28%) to their interaction. Additive interaction among men was smaller although still significant (p interaction 0.002, p for heterogeneity 0.04 between women and men), and attributable proportion of joint effect was 14% (6% to 22%).ConclusionsWhile excess adiposity and genetic predisposition both are strongly associated with a higher risk of gout, the excess risk of both combined was higher than the sum of each, particularly among women.

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Association of a Notch 3 gene polymorphism with migraine susceptibility

Cephalalgia ◽

10.1177/0333102410381143 ◽

2010 ◽

Vol 31 (3) ◽

pp. 264-270 ◽

Cited By ~ 16

Author(s):

S Menon ◽

HC Cox ◽

M Kuwahata ◽

S Quinlan ◽

JC MacMillan ◽

...

Keyword(s):

Single Nucleotide Polymorphisms ◽

Gene Polymorphism ◽

Migraine Without Aura ◽

Autosomal Dominant ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Follow Up Study ◽

Notch 3

Introduction: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) shares common symptoms with migraine. Most CADASIL causative mutations occur in exons 3 and 4 of the Notch 3 gene. This study investigated the role of C381T (rs 3815188) and G684A (rs 1043994) single nucleotide polymorphisms (SNP) in exons 3 and 4, respectively, of the Notch 3 gene in migraine. Results: The first part of the study, in a population of 275 migraineurs and 275 control individuals, found a significant association between the C381T variant and migraine, specifically in migraine without aura (MO) sufferers. The G684A variant was also found to be significantly associated with migraine, specifically in migraine with aura (MA) sufferers. A follow-up study in 300 migraineurs and 300 control individuals did not show replicated association of the C381T variant with migraineurs. However, the G684A variant was again shown to be significantly associated with migraine, specifically with MA. Conclusion: Further investigation of the G684A variant and the Notch 3 gene is warranted to understand their role in migraine.

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Association of genetic polymorphism of cytokines and antioxidant enzymes with the development of asbestosis

Russian Journal of Occupational Health and Industrial Ecology ◽

10.31089/1026-9428-2020-60-12-898-903 ◽

2020 ◽

Vol 60 (12) ◽

pp. 898-903

Author(s):

Lyudmila P. Kuzmina ◽

Anastasiya G. Khotuleva ◽

Evgeniy V. Kovalevsky ◽

Nikolay N. Anokhin ◽

Iraklij M. Tskhomariya

Keyword(s):

Antioxidant Enzymes ◽

Genetic Polymorphism ◽

Genetic Predisposition ◽

Risk Groups ◽

Dust Exposure ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Gstp1 Gene ◽

Polymorphic Variants

Introduction. Various industries widely use chrysotile asbestos, which determines the relevance of research aimed at the prevention of asbestos-related diseases. It is promising to assess the role of specific genes, which products are potentially involved in the development and regulation of certain links in the pathogenesis of asbestosis, forming a genetic predisposition to the disease. The study aims to analyze the presence of associations of genetic polymorphism of cytokines and antioxidant enzymes with asbestosis development. Materials and methods. Groups were formed for examination among employees of OJSC "Uralasbest" with an established diagnosis of asbestosis and without lung diseases. For each person included in the study, dust exposure doses were calculated considering the percentage of time spent at the workplace during the shift for the entire work time. Genotyping of single nucleotide polymorphisms of cytokines IL1b (rs16944), IL4 (rs2243250), IL6 (rs1800795), TNFα (rs1800629) and antioxidant enzymes SOD2 (rs4880), GSTP1 (rs1610011), CAT (rs1001179) was carried out. Results. The authors revealed the associations of polymorphic variants A511G IL1b gene (OR=2.457, 95% CI=1.232-4.899) and C47T SOD2 gene (OR=1.705, 95% CI=1.055-2.756) with the development of asbestosis. There was an increase in the T allele IL4 gene (C589T) frequency in persons with asbestosis at lower values of dust exposure doses (OR=2.185, 95% CI=1.057-4.514). The study showed the associations of polymorphism C589T IL4 gene and C174G IL6 gene with more severe asbestosis, polymorphism A313G GSTP1 gene with pleural lesions in asbestosis. Conclusion. Polymorphic variants of the genes of cytokines and antioxidant enzymes, the protein products directly involved in the pathogenetic mechanisms of the formation of asbestosis, contribute to forming a genetic predisposition to the development and severe course of asbestosis. Using the identified genetic markers to identify risk groups for the development and intense period of asbestos-related pathology will optimize treatment and preventive measures, considering the organism's characteristics.

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