Replication association studyIREB2, CHRNA5, CHRNA3, CHRNB4, FAM13A, HTR4, andHHIPgenes polymorphisms with chronic obstructive pulmonary disease in Tatar population from Russia

Abstract

Background and objective: Genome-wide association studies (GWASs) have identified several loci associated with chronic obstructive pulmonary disease (COPD). This work was designed as a replication study aimed at investigating the association of COPD with IREB2, CHRNA5, CHRNA3, CHRNB4, FAM13A, HTR4 , and HHIP in Tatar population from Russia. Methods: SNPs ( rs13180, rs16969968, rs1051730, rs1948, rs6495309, rs7671167, rs3995090 rs13118928 ) were genotyped with the TaqMan assays in a case-control study (511 COPD patients and 508 control, ethnic Tatars from Ufa, Russia). Logistic regression was used to detect the association of SNPs and haplotypes of linked loci in different models. Linear regression analyses were performed to estimate the relationship between SNPs and lung function parameters and pack-years. Results: The rs13180, rs16969968 , and rs1051730 were significantly associated with COPD in additive model ( P adj = 0.00001, OR = 0.64; P adj = 0.0001, OR = 1.41 and P adj = 0.0001, OR = 1.47). The C-G haplotype by rs1318 0 and rs1051730 was a protective factor for COPD in our population (P adj =0.0005, OR=0.61). The rs13180, rs16969968, rs1051730 , and rs3995090 were significantly associated with COPD only in smokers. The rs16969968 and rs1051730 were associated with decrease of FEV1% predicted (P adj =0.005 and P adj =0.0019). We found a significant gene-by-environment interaction of smoking status and HTR4 (rs3995090) (P interact =0.016). Conclusion: Our study confirmed the association of rs13180, rs16969968, rs3995090, and rs1051730 with COPD and lung function in Tatar population from Russia.