Methodological strategies for mapping HLA susceptibility loci in vitiligo: A focused minireview

Table 1 Main study designs in vitiligo

Type of study	Unit of study	Common techniques
HLA expression	HLA protein levels	Flow cytometry, immunohistochemistry
	HLA mRNA levels	qPCR, RNA-seq, microarray
Case-control	Unrelated case-control, exposure and non-exposure group	Microlymphocytotoxicity, SSP, SSO, qPCR, PCR-RFLP, microarray, SBT, and NGS
Family-based association	Related-case control	SSP, SSO
GWAS	Unrelated case-control, exposure and non-exposure group	RNA-seq, microarray

GWAS: Genome-wide association studies; PCR: Polymerase chain reaction; SSP: Sequence-specific primer; SSO: Sequence-specific oligonucleotide; RFLP: Restriction fragment length polymorphism; SBT: Sequence-based typing; NGS: Next-generation DNA sequencing; RNA-seq: RNA sequencing.

Table 2 HLA haplotypes associated with vitiligo and the study population

HLA haplotypes	Controls	Vitiligo	Haplotype estimation	P value	Risk	Study population
DRB1*07–DQB1*02	300	100	EM algorithm	Pc = 0.024	Predisposing	Moroccan[27]
DRB1*03–DQB1*02				Pc = 0.012	Protective
A*02-B*51-C*15-DRB1*07-DQB1*02	243	116	EM algorithm	P = 0.0113	Predisposing	Brazilian[34]
A*02-B*15-C*07-DRB1*13-DQB1*06				P = 0.0340	Predisposing
A*29-B*44-C*16-DRB1*07-DQB1*02				P = 0.0340	Predisposing
A*33:01-DRB1*07:01	29	251	EM algorithm	P = 6.97 × 10-26	Predisposing	North India[32]
DRB1*04– DQB1*0301	3798	76	Family-based studies	Pc < 0.003	Predisposing	White European and American[59]
DRB1*15–DQB1*0602				Pc < 0.003	Protective
A25-B13-Cw*0602	273	187	Direct counting	P = 0.00166	Predisposing	Chinese[58]
A25-B27-Cw*0602				P = 0.00032	Predisposing
DQA1*0302-DQB1*0303-Cw*0602				P = 0.02300	Predisposing
B13-DQB1*0303-Cw*0602				P = 0.00380	Predisposing

Pc: Corrected P value; HLA: Human leukocyte antigen; EM: Expectation–maximization.