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Am J Respir Crit Care Med. 2007 Mar 15;175(6):554-60. Epub 2007 Jan 4.

Secreted modular calcium-binding protein 2 haplotypes are associated with pulmonary function.

Author information

1
Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA.

Abstract

RATIONALE:

Previously reported linkage to FEV(1) (LOD score = 5.0) on 6q27 in the Framingham Heart Study (FHS) led us to explore a candidate gene, SMOC2, at 168.6 Mb.

OBJECTIVES:

We tested association between SMOC2 polymorphisms and FEV(1) and FVC in unrelated FHS participants.

METHODS:

Twenty single-nucleotide polymorphisms (SNPs) around SMOC2 were genotyped in 1,734 subjects.

MEASUREMENTS AND MAIN RESULTS:

SNP data were analyzed using multiple linear regression models incorporating sex, age, body mass index, height, and smoking history as covariates, and analyses were repeated within strata of ever- and never-smokers. The minor allele of SNP rs1402 was associated with higher mean FEV(1) (p = 0.003) and FVC (p = 0.02) measures. In never-smoking subjects, association with higher measures was observed with the minor allele of rs747995 (FEV(1), p = 0.0006; FVC, p = 0.0008). These two SNPs lie in different haplotype blocks and reside in intron 4 of SMOC2. Haplotype analysis revealed a common G-T haplotype (rs747995-rs1402) with 77% frequency in never-smoking FHS subjects. The G-T haplotype was associated with reduction of 126 ml for FEV(1) (p = 0.0002) and 157 ml for FVC (p = 0.0002). The G-T haplotype was similarly associated in a set of never-smoking subjects from the Family Heart Study (FEV(1), p = 0.03; FVC, p = 0.03).

CONCLUSIONS:

The replication of the association in two populations supports the possibility that SMOC2 might play an important role in the determination of FEV(1) and FVC.

PMID:
17204727
PMCID:
PMC1899283
DOI:
10.1164/rccm.200601-110OC
[Indexed for MEDLINE]
Free PMC Article

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