Do Polynesians have a higher risk of HLA-B*5801 (Human Leukocyte Antigen B*5801) allele defects?

HLA-B*5801 Prevalence in Polynesians and Risk for Allopurinol Hypersensitivity

Based on current evidence, there is insufficient data specifically documenting the prevalence of HLA-B*5801 in Polynesian populations, but recent research suggests Filipinos in Hawaii have a high prevalence (7.2%) comparable to other high-risk Asian populations, indicating Polynesians may have similar elevated risk. 1

HLA-B*5801 Prevalence in Different Populations

• HLA-B*5801 allele frequencies vary significantly across ethnic groups, with highest prevalence in:

  • Han Chinese, Thai, and Korean populations (6-15%) 2
  • Filipino patients in Hawaii (7.2%) 1
  • African Americans (3.8%) 2
  • Europeans and Hispanics (much lower at approximately 0.7-2%) 2

• While specific data for Polynesians is limited, the high prevalence in Filipinos in Hawaii suggests that other Pacific Islander populations may have similar elevated frequencies 1

Clinical Significance of HLA-B*5801

• HLA-B*5801 is the strongest risk factor for allopurinol-induced severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) 2

• The association between HLA-B*5801 and allopurinol-induced SCARs is particularly strong in Asian populations with hazard ratios of several hundred 2

• The risk of developing SCARs is significantly increased when HLA-B*5801 is present:

  • Odds ratio of 348.3 in Thai populations (95% CI: 19.2-6336.9) 3
  • Odds ratio of 49.0 in Malaysian multiethnic populations (95% CI: 14.6-164.4) 4

Current Screening Recommendations

• The 2020 American College of Rheumatology conditionally recommends HLA-B*5801 testing prior to starting allopurinol for:

  • Patients of Southeast Asian descent (Han Chinese, Korean, Thai)
  • African American patients 2

• The 2012 ACR guidelines specifically recommended HLA-B*5801 screening in:

  • Korean patients with stage 3 or worse chronic kidney disease (CKD)
  • All patients of Han Chinese or Thai descent regardless of renal function 2

• The 2017 EULAR guidelines do not recommend systematic HLA-B*5801 screening but acknowledge the genetic risk and leave testing to physician discretion 2

Risk Factors and Clinical Implications

• The risk of allopurinol-induced SCARs is significantly increased when HLA-B*5801 is combined with renal impairment:

  • Heterozygous HLA-B*5801 with normal renal function: OR = 15.25
  • Homozygous HLA-B*5801 with severe renal impairment: OR = 1269.45 5

• Recent evidence suggests that genotyping may be beneficial in Filipino patients in Hawaii due to the high prevalence (7.2%) of HLA-B*5801 1

Recommendations for Polynesian Patients

• Given the high prevalence of HLA-B5801 in Filipino patients in Hawaii (7.2%), which is comparable to other high-risk Asian populations, HLA-B5801 testing should be considered before initiating allopurinol in Polynesian patients 1, 2

• For Polynesian patients with chronic kidney disease, the risk of allopurinol-induced SCARs may be further elevated, making HLA-B*5801 testing particularly important in this subgroup 5, 6

• If HLA-B*5801 testing is positive in Polynesian patients, alternative urate-lowering therapies such as febuxostat should be considered 2

Limitations and Caveats

• The specific prevalence of HLA-B*5801 in many Polynesian subpopulations remains understudied 1

• Cost-effectiveness of universal HLA-B*5801 screening depends on the prevalence in the population and may not be justified in populations with very low prevalence 2

• When HLA-B*5801 testing is not available or feasible, careful monitoring for early signs of hypersensitivity reactions and patient education about symptoms requiring immediate medical attention are essential 2