Hyperuricemia (HU) has been identified as an important predictor in the development of gout. Studies have indicated that specific racial and ethnic subgroups tend to have a distinct prevalence of HU and gout, and thus, that the frequency of HU and gout alleles varies across these subgroups. “Many factors play different roles in regulating serum urate levels and might lead to HU and gout,” explains Youssef Roman, PharmD, PhD.


Estimating the Frequency of HU & Gout Risk Alleles in Subgroups

Studies have identified a link between genetic polymorphisms in urate disposition and the incidence of gout among different ethnic groups. In previous research, single nucleotide polymorphisms (SNPs) have been implicated in the development of HU or gout. For a study published in BMC Rheumatology, Dr. Roman and colleagues estimated the frequency of HU and gout risk alleles in Asian, Native Hawaiian, and Pacific Islander subgroups using biorepository DNA samples.

“We wanted to estimate the frequencies of selected SNPs in specific urate genes across Filipino, Japanese, Korean, Samoan, Marshallese, and Native Hawaiian patients and compared them with the European population,” Dr. Roman says. “To our knowledge, this is one of the first studies to explore population-specific risk in these subgroups. Our goal was to increase our understanding of the genetics of HU and gout in these under-represented populations.” For the study, DNA samples were analyzed in 1,059 post-partum women aged 18 and older. Asian subgroups included Japanese, Filipino, and Korean patients, whereas Pacific Islander subgroups included Marshallese and Samoan patients. “Importantly, none of the participants in our study had a history of gout,” says Dr. Roman.

The authors selected nine urate genes to review—ABCG2, SLC2A9, SLC16A9, GCKR, SLC22A11, SLC22A12, LRR16A, PDZK1, and SLC17A1—based on their significant association with HU and gout risk. The PDZK1 gene was ultimately excluded from the final analysis because it deviated from Hardy-Weinberg equilibrium across all subgroups, leaving eight loci for cross-subgroup comparisons. Allele frequencies were then compared with those of the European population.


HU & Gout Risk Alleles More Frequent in Asian Subgroups

HU and gout risk alleles were significantly more frequent among Asian subgroups than in the European population. When compared with those of Europeans, genetic polymorphism frequencies were different across racial/ethnic subgroups (Table). Compared with that of Europeans, the frequency of the eight loci in patients of Japanese and Samoan were statistically different, whereas only six loci in Korean, Filipino, Native Hawaiian, and Marshallese descent were statistically different. The HU and gout risk alleles indices were 8, 6, 5, 5, 4, and 4 in Japanese, Filipino, Korean, Samoan, Marshallese, and Native Hawaiian patients, respectively.

“Post-partum women of Asian ancestry had a higher prevalence of HU or gout risk alleles when compared with the European population,” says Dr. Roman. “Of note, the significantly different uric acid alleles observed in the Japanese and Filipino cohorts were all considered HU or gout risk alleles compared with Europeans. These results suggest that genetic makeup could partially explain differences in the prevalence of HU and gout across ethnic and racial groups. The results may also explain the gout risk penetrance among selected population groups when accustomed to a western diet.”


Genetic Data Might Improve Risk Prediction & Guide Treatment

According to Dr. Roman, the findings provide more evidence that individuals of Asian descent have a higher risk for gout and for having high-risk alleles than Europeans. “Our study is among the first to break down the parallelism between HU, gout, and genetics in these subgroups of pregnant women,” he says. “Based on our results, genetic assessments could play an important role in addressing ongoing gout health disparities. By assessing genetics, we can potentially predict who may develop the disease based on genetic markers. Our data can also be used to predict disease progression and select proper treatment to improve patient outcomes. Furthermore, these data may inform future research on the effects of hormonal changes during pregnancy on urate gene expression and the role of HU and gout risk alleles in pregnancy outcomes, such as gestation diabetes, gestation hypertension, and preeclampsia.”