Association between ADAM33 gene polymorphisms and asthma in the Zhuang population of China

To explore the potential association between five single nucleotide polymorphisms (SNPs) (rs44707, rs612709, rs598418, rs2280089, and rs574174) in the ADAM33 gene and asthma susceptibility in the Zhuang population of Guangxi, China.

A single-center case-control study was conducted involving 155 asthma patients and 106 healthy controls. Genotyping of the five ADAM33 SNPs were performed using multiplex PCR capture and next-generation sequencing. Association analyses of genotype, allele, and haplotype distributions were conducted, with adjustments for potential confounding factors (age, sex, height, and weight) and Bonferroni correction for multiple testing. Hardy-Weinberg equilibrium (HWE) was verified in the control group to assess population representativeness.

The genotype distributions of all five SNPs in the control group were consistent with HWE (P > 0.05). Before covariate adjustment, significant differences were observed between the case and control groups in the genotype and allele frequencies of rs44707 (genotype: χ² = 7.180, P = 0.028; allele: χ² = 5.344, P = 0.021), rs612709 (genotype: χ² = 6.548, P = 0.029; allele: χ² = 7.060, P = 0.008), and rs598418 (genotype: χ² = 8.750, P = 0.013; allele: χ² = 7.607, P = 0.006). No significant differences were found in the genotype or allele frequencies of rs2280089 and rs574174 between the two groups (P > 0.05). After adjusting for covariates, multiple genetic models (allele, homozygous, recessive) of rs44707, rs612709, and rs598418 still showed significant associations with asthma (P < 0.05). After Bonferroni correction, allele frequency differences retained significance for rs612709 (P_adj = 0.040) and rs598418 (P_adj = 0.030), but not for rs44707 (genotype P_adj = 0.140; allele P_adj = 0.105). Haplotype analysis revealed that the frequency of the GGGGC haplotype was significantly higher in the case group than in the control group (χ² = 6.177, OR = 1.603, 95 % CI: 1.104-2.329, P = 0.013), but this significance was not retained after Bonferroni correction (P_adj = 0.065).

This study provides preliminary evidence that rs44707, rs612709, and rs598418 in the ADAM33 gene may be associated with asthma susceptibility in the Zhuang population of Guangxi. The GGGGC haplotype shows a trend of potential association with increased asthma risk, but this finding requires further verification. Given limitations of single-center design, small sample size, these observations require cautious interpretation. Larger multi-center studies with stratified cohorts and functional validation are needed to confirm the role of ADAM33 genetic variants in asthma among this ethnic group.