Integrated Analysis of the Association Between Variants at PAX7 and NSCL/P in the Han Population

Abstract

Objective Paired box 7 ( PAX7) has been considered as a candidate gene for non-syndromic cleft lip with or without palate (NSCL/P). However, there is no research for the XXX, and previous studies concentrated on limited variants. This study aimed to conduct sufficiently dense and powerful scans of variants at PAX7 and explored the roles of variants at PAX7 in NSCL/P among the XXX. Design Targeted region sequencing was performed to thoroughly screen variations, followed by a two-phase association analysis. 159 NSCL/P cases and 542 controls were analyzed in phase 1. Then in phase 2, the validation study was performed using 1626 cases and 2255 controls. We also explored the roles of variants at PAX7 gene in NSCL/P subtypes. Additionally, indirect associations were found by calculating LD and haplotypes. Setting The study was conducted in XXX. Patients, participants 159 NSCL/P cases and 542 controls were analyzed in phase 1. Then in phase 2, the validation study was performed using 1626 cases and 2255 controls. Interventions Blood samples were collected. Main outcome measures To explore the association analysis between variants at PAX7 and NSCL/P in XXX. Results The results showed that rs2236810, rs114882979 and rs2236804 were significantly associated with NSCL/P, which were predicted to have regulatory functions. Besides, variants at PAX7 function differently in the NSCL/P subtypes. We also discovered a PAX7 missense variant, NM_001135254 p.A369 V (NM_002584.2:c.1106C > T). Conclusions In summary, we confirmed 3 SNPs at PAX7 were significantly associated with NSCL/P in XXX and identified a missense variant, NM_001135254 p.A369 V (NM_002584.2:c.1106C > T).