An exploratory genome-wide association study of leprosy susceptibility genes in a Thai cohort

Sukanya Wattanapokayakit; Ekawat Pasomsub; Punna Kunhapan; Suphannee Phatsadon; Punnarai Veeraseatakul; Krisada Mahotarn; Taisei Mushiroda

ผู้แต่ง

Sukanya Wattanapokayakit 1 Medical Life Sciences Institute, Department of Medical Sciences, Ministry of Public Health, Nonthaburi
Ekawat Pasomsub Faculty of Medicine Ramathibodi Hospital, Mahidol University
Punna Kunhapan Medical Life Sciences Institute, Department of Medical Sciences, Ministry of Public Health, Nonthaburi
Suphannee Phatsadon Sirinthorn Hospital, Ministry of Public Health, Nonthaburi
Punnarai Veeraseatakul Regional Medical Sciences Center 1 Chiang Mai, Department of Medical Sciences, Ministry of Public Health, Chiang Mai
Krisada Mahotarn Rajprachasamasai Institute, Department of Disease Control, Ministry of Public Health, Samut Prakan
Taisei Mushiroda Center for Genomic Medicine, RIKEN Yokohama Campus, Yokohama City, Kanagawa

คำสำคัญ:

Leprosy, Genome-wide association studies, GWAS

บทคัดย่อ

Leprosy is a chronic granulomatous infectious disease caused by Mycobacterium leprae. Although candidate gene studies have explored genetic susceptibility to leprosy, only a limited number of genomic loci have been independently replicated. In contrast, genome-wide association studies (GWAS) have provided clear evidence that host genetic factors—varying across different ethnic populations—play a critical role in determining human susceptibility to infection and in influencing the progression of infectious diseases. We performed genome-wide association study involving 344 individuals with leprosy - 103 with paucibacillary form and 241 multibacillary form - and 200 control individuals, using the Illumina Ommi express platform. This study highlights a potential genome-wide association signal for leprosy on chromosome 18 (18q21.33–18q22.1) supported by suggestive evidence (P-values<1×10^-5). Within this region, the lead variant rs9949621 demonstrated the strongest association (P-values<4.75×10^-6, Odds Ratio [OR] = 0.53, 95% Confidence Interval [CI] = 0.40-0.70) and is located near the HMSD gene. The association peak extended across a broader region encompassing several SERPIN family genes (SERPINB2, SERPINB10, HMSD, and SERPINB8), where multiple single nucleotide polymorphisms (SNPs) consistently showed P-values below 5.0×10⁻⁵. Collectively, this suggests that variants within this gene cluster may influence genetic susceptibility to leprosy. Importantly, all associated SNPs appeared to confer a protective effect, as the minor alleles were more frequent in controls than in cases, indicating reduced disease risk in carriers. Our genome-wide association study (GWAS) suggests a potential novel link between HMSD and several genes within the SERPIN family and susceptibility to leprosy in the Thai population. While these results highlight a promising genetic association, they will need to be confirmed through independent replication studies and supported by functional investigations. Additional high-resolution genotyping or sequencing analyses will also be necessary to refine these findings and clarify their biological significance.

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