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


OBJECTIVE
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.


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.
Wilk
Jemma B
JB
Department of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA.
Herbert
Alan
A
Shoemaker
Christina M
CM
Gottlieb
Daniel J
DJ
Karamohamed
Samer
S
D002135:Calcium-Binding Proteins / Q000235:genetics*; D005541:Forced Expiratory Volume / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007438:Introns; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000453:epidemiology; D014797:Vital Capacity / Q000235:genetics*
D002135:Calcium-Binding Proteins; C476827:SMOC2 protein, human