Lack of association of the PLD4 SNP rs2841277 with systemic sclerosis in a European American population

This study aimed to examine whether a reported SSc-associated SNP rs2841277 in the PLD4 gene identified in an Asian population was also associated with SSc in European American (EA). The EA cohort consisting of 1005 SSc patients and 961 healthy controls was examined in this study. TaqMan genotyping assays were performed to examine the SNP. Exact P-values were obtained from 2 x 2 tables of allele counts and disease status. In contrast to the previous reports in a Japanese population, SSc patients of EA did not show an association of PLD4 rs2841277 with SSc in general (P = 0.231, OR = 0.89, 95% CI = 0.73-1.08), or with clinical subtypes of dcSSc (P = 0.302, OR = 0.86, 95% CI = 0.65-1.13) and lcSSc (P = 0.369, OR = 0.90, 95% CI = 0.72-1.12), or with autoantibody subtypes including ATA (P = 0.126, OR = 0.74, 95% CI = 0.51-1.08), ACA (P = 0.943, OR = 1.01, 95% CI = 0.77-1.34), ARP3 (P = 0.155, OR = 0.77, 95% CI = 0.53-1.1), or Anti-RNP (P = 0.660, OR = 0.73, 95% CI = 0.29-1.84). We found a lack of association of the PLD4 SNP rs2841277 with SSc in an EA population. This is the first study to report a discrepancy in the genetic association between the PLD4 SNP and SSc. This may be explained by genetic heterogeneity between Japanese and EA populations, with genetic ancestry contributing to this variation. Further verification in diverse ancestral populations is warranted.