The genetic basis of gout.

Gout results from deposition of monosodium urate (MSU) crystals. Elevated serum urate concentrations (hyperuricemia) are not sufficient for the development of disease. Genome-wide association studies (GWAS) have identified 28 loci controlling serum urate levels.

Association of autoimmune Addison's disease with alleles of STAT4 and GATA3 in European cohorts.

Background: Gene variants known to contribute to Autoimmune Addison's disease (AAD) susceptibility include those at the MHC, MICA, CIITA, CTLA4, PTPN22, CYP27B1, NLRP-1 and CD274 loci. The majority of the genetic component to disease susceptibility has yet to be accounted for.

Aim: To investigate the role of 19 candidate genes in AAD susceptibility in six European case-control cohorts.

The global burden of gout: estimates from the Global Burden of Disease 2010 study.

Objective: Gout is the most common cause of inflammatory arthritis in men, but has not previously been included in Global Burden of Disease (GBD) studies. As part of the GBD 2010 Study, the Musculoskeletal Disorders and Risk Factors Expert Group estimated the global burden of gout.

Methods: The American Rheumatism Association 1977 case definition of primary gout was used in the study.

Sugar-sweetened beverages, urate, gout and genetic interaction.

The clinical manifestations of gout occur as a result of immune responses to monosodium urate crystals. Elevated serum levels of urate (hyperuricemia) are a prerequisite for the development of gout with reduced fractional renal excretion of uric acid (FEUA) an important cause. In New Zealand, Mãori and Pacific Island people have inherently raised urate levels with one consequence a higher prevalence of more severe gout.

An 'end-game' for sugar sweetened beverages?

Objective: The epidemic of unhealthy weight is now in its third decade. The multitude of initiatives designed to address this issue (globally) have predominantly been ineffective as the prevalence of unhealthy weight has continued to rise. Public health professionals have proposed an 'endgame' for tobacco smoking in New Zealand by 2025, which has received widespread support.

Fat storage syndrome in Pacific peoples: a combination of environment and genetics?

Pacific people (especially Micronesian and Polynesian) have some of the highest rates of obesity and diabetes in the world that largely developed since the introduction of western culture and diet. Recent studies suggest that much of the risk relates to the excessive intake of sugar (sucrose) and carbohydrates, leading to a type of fat storage syndrome (metabolic syndrome). Here we discuss some of the environmental.

A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides.

Introduction: Rheumatoid arthritis (RA) patients can be classified based on presence or absence of anticitrullinated peptide antibodies (ACPA) in their serum. This heterogeneity among patients may reflect important biological differences underlying the disease process. To date, the majority of genetic studies have focused on the ACPA-positive group.

Influence of the ABCG2 gout risk 141 K allele on urate metabolism during a fructose challenge.

Introduction: Both genetic variation in ATP-binding cassette sub-family G member 2 (ABCG2) and intake of fructose-containing beverages are major risk factors for hyperuricemia and gout. This study aimed to test the hypothesis that the ABCG2 gout risk allele 141 K promotes the hyperuricaemic response to fructose loading.

Methods: Healthy volunteers (n = 74) provided serum and urine samples immediately before and 30, 60, 120 and 180 minutes after ingesting a 64 g fructose solution.

Myeloid-related proteins 8 and 14 contribute to monosodium urate monohydrate crystal-induced inflammation in gout.

Objective: Monosodium urate monohydrate (MSU) crystal-induced interleukin-1β (IL-1β) secretion is a critical factor in the pathogenesis of gout. However, without costimulation by a proIL-1β-inducing factor, MSU crystals alone are insufficient to induce IL-1β secretion. The responsible costimulatory factors that act as a priming endogenous signal in vivo are not yet known.

Hyperuricaemia in the Pacific: why the elevated serum urate levels?

Pacific Island populations, particularly those of Polynesian descent, have a high prevalence of hyperuricaemia and gout. This is due to an inherently higher urate level among these populations with a demonstrated genetic predisposition. While an excess of urate can cause pathology, urate is also important for human health.

Association analysis of the SLC22A11 (organic anion transporter 4) and SLC22A12 (urate transporter 1) urate transporter locus with gout in New Zealand case-control sample sets reveals multiple ancestral-specific effects.

Introduction: There is inconsistent association between urate transporters SLC22A11 (organic anion transporter 4 (OAT4)) and SLC22A12 (urate transporter 1 (URAT1)) and risk of gout. New Zealand (NZ) Māori and Pacific Island people have higher serum urate and more severe gout than European people. The aim of this study was to test genetic variation across the SLC22A11/SLC22A12 locus for association with risk of gout in NZ sample sets.

Prevalence of HLA-B27 in the New Zealand population: effect of age and ethnicity.

Introduction: HLA-B27 genotyping is commonly used to support a diagnosis of ankylosing spondylitis (AS). A recent study has suggested that HLA-B27 may adversely affect longevity. The objectives of this study were to determine, for the first time, the prevalence of HLA-B27 in the New Zealand population, and to test whether HLA-B27 prevalence declines with age.

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

Introduction: 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 Māori study cohort from the East Coast region of NZ's North Island.

Macrophage migration inhibitory factor gene polymorphisms in inflammatory bowel disease: an association study in New Zealand Caucasians and meta-analysis.

Aim: To investigate the association of macrophage migration inhibitory factor (MIF) promoter polymorphisms with inflammatory bowel disease (IBD) risk.

Methods: One thousand and six New Zealand Caucasian cases and 540 Caucasian controls were genotyped for the MIF SNP -173G > C (rs755622) and the repeat polymorphism CATT₅₋₈ (rs5844572) using a pre-designed TaqMan SNP assay and capillary electrophoresis, respectively. Data were analysed for single site and haplotype association with IBD risk and phenotype.

Mendelian randomization analysis associates increased serum urate, due to genetic variation in uric acid transporters, with improved renal function.

Increased serum urate predicts chronic kidney disease independent of other risk factors. The use of xanthine oxidase inhibitors coincides with improved renal function. Whether this is due to reduced serum urate or reduced production of oxidants by xanthine oxidase or another physiological mechanism remains unresolved.

Sugar-sweetened beverage consumption: a risk factor for prevalent gout with SLC2A9 genotype-specific effects on serum urate and risk of gout.

Objective: Consumption of high fructose corn syrup (HFCS)-sweetened beverages increases serum urate and risk of incident gout. Genetic variants in SLC2A9, that exchanges uric acid for glucose and fructose, associate with gout. We tested association between sugar (sucrose)-sweetened beverage (SSB) consumption and prevalent gout.

Systematic review of the prevalence of gout and hyperuricaemia in Australia.

Aims: Gout is a growing health problem worldwide especially in affluent countries, such as Australia. Gout and hyperuricaemia are associated with the metabolic syndrome, diabetes mellitus, obesity and hypertension. More importantly, Australia has a growing prevalence of these important health problems.

Association of the HLA locus and TNF with type I autoimmune hepatitis susceptibility in New Zealand Caucasians.

Purpose: The precise etiology of autoimmune hepatitis (AIH) remains unknown, although a number of genetic loci have been implicated in the susceptibility of type 1 AIH. The purpose of this study was to test for association of these loci with type 1 AIH in New Zealand Caucasians.

Methods: 77 AIH patients and 485 healthy controls were genotyped for the SNPs rs2187668 (HLA-DRB*03:01), rs660895 (HLA-DRB*04:01), rs3749971 (HLA-A1-B8-DR3), rs231775 (CLTLA4), rs1800629 (TNF), and rs1800682 (FAS) using predesigned TaqMan SNP genotyping assays.

Frequency of CYP2C9 polymorphisms in Polynesian people and potential relevance to management of gout with benzbromarone.

Objectives: Gout is a major health problem in Polynesians and allopurinol, the drug of choice for the management gout, appears to be less effective in Polynesian patients. The uricosuric drug benzbromarone is an alternative treatment but CYP2C9 poor metabolisers (PMs) may be at a heightened risk of benzbromarone-induced hepatotoxicity. The objectives of this study were to determine the frequency of the PM alleles CYP2C9*2 and CYP2C9*3 in New Zealand (NZ) Caucasian and Polynesian gout cohorts; and then to test for novel CYP2C9 polymorphisms in Polynesians.

Association of CD247 polymorphisms with rheumatoid arthritis: a replication study and a meta-analysis.

Given the role of CD247 in the response of the T cells, its entailment in autoimmune diseases and in order to better clarify the role of this gene in RA susceptibility, we aimed to analyze CD247 gene variants previously associated with other autoimmune diseases (rs1052237, rs2056626 and rs864537) in a large independent European Caucasian population. However, no evidence of association was found for the analyzed CD247 single-nucleotide polymorphisms (SNPs) with RA and with the presence/absence of anti-cyclic citrullinated polypeptide. We performed a meta-analysis including previously published GWAS data from the rs864537 variant, revealing an overall genome-wide significant association between this CD247 SNP and RA with anti-CCP (OR = 0.

CNVrd, a read-depth algorithm for assigning copy-number at the FCGR locus: population-specific tagging of copy number variation at FCGR3B.

The extent of contribution from common gene copy number (CN) variants in human disease is currently unresolved. Part of the reason for this is the technical difficulty in directly measuring CN variation (CNV) using molecular methods, and the lack of single nucleotide polymorphisms (SNPs) that can tag complex CNV that has arisen multiple times on different SNP haplotypes. One CNV locus implicated in human disease is FCGR.