Association of HLA‐DR3 and HLA‐DR4 with Sinonasal Polyposis in Mexican Mestizos

Abstract

B-2b.

Genetics of chronic rhinosinusitis: State of the field and directions forward

“…45, 46, 57, 80-84 However, there remains no consensus, as few attempts have been made to replicate these associations. To give one example of the complexity of comparing studies, the haplotype HLA-A1/B8 has been examined in two populations, a case series of 29 CRSwNP subjects from the United Kingdom (UK) by Moloney et al 81 and an Austrian case-control study of 89 CRSwNP subjects and 1070 controls by Luxenberger et al 80 Neither study found HLA-A1/B8 to be associated with CRSwNP itself.…”

“…45, 46 In a study of Mexican Mestizos (defined as having mixed Native American [56%], European [40%], and African [4%] ancestry) involving 34 CRSwNP patients and 99 controls, Ramirez-Anguiano et al 45 found the HLA-DRB1*04 allele was significantly associated with CRSwNP (odds ratio [OR]=2.2, 95% confidence interval [CI]=1.2-4.2, P = .009). However, a Turkish study of 66 CRSwNP patients and 100 controls by Keles et al 46 did not find HLA-DRB1*04 to be more frequent in CRSwNP patients compared to controls (allele frequency [AF] in CRSwNP=23.4%, AF in controls=23.4%, P > .05).…”

“…46 Of note, none of the CRSwNP patients in the study of Mexican Mestizos had AERD, and only four patients (12%) had asthma. 45 These differences suggest HLA-DRB1*04 may be associated with distinct CRS phenotypes (e.g., with or without asthma or AERD) in different populations.…”

“…For example, many studies that reported negative findings were underpowered, so the genes examined cannot be excluded as candidates for involvement in CRS. Studies that reported positive associations often had limited phenotyping (e.g., the unclear importance of AERD in the association between CRS and HLA-DRB1*04 45, 46 ) or included a heterogeneous phenotype (e.g., CRSwNP, CRSsNP, and RARS combined 150 ). In some sense, this could be an advantage because SNPs identified might be involved in all these disease categories, but there is also no ability to determine SNPs affecting individual disease subphenotypes.…”

Can HLA-DRB4 Help to Identify Asthmatic Patients at Risk of Churg-Strauss Syndrome?

“…Particularly, HLA-DRB1 genes have been involved in asthma severity in children [5, 6] and susceptibility to occupational asthma [7] and allergic bronchopulmonary aspergillosis [8]. They are implicated also in nasal polyposis and, in particular, the HLA-DRB1∗04 allele has been associated with sinonasal polyposis in a study on the Mexican Mestizo population [13] and in a group of Turkish patients with nasal polyposis, asthma, and aspirin salicylic acid triad [14]. …”