Introduction Smoking is associated with accelerated decline in lung function. However, smoking and lung function decline donothaveatypicallinearrelationshipassuggestedby thefactthatonly15-20%ofallsmokersdevelopchronic obstructive pulmonary disease (COPD). Thus there may be genetic factors that modulate the expression of smoking on lung function decline. One interesting but understudied molecule in the pathogenesis of smoking-related lung disease is surfactant protein D (SFTPD). SFTPD is a complex pneumoprotein that is involved primarily in innate immune response of the lung. 1 It modulates macrophage function to carefully orchestrate the inflammatory response against aero- pathogens and irritants. It also plays an important role in turning off the inflammatory response once the pathogens have been neutralised, thus limiting collateral damage from inflammatory and oxidative stress. 2-5 ThehumanSFTPDgeneisassociatedwithmultiplesingle nucleotide polymorphisms (SNPs) in protein coding as well as non-coding regions. For instance, SNP rs721917 causes amino acid substitution in N terminal domain of thematureproteinwhereasrs3088308substitutesamino acids in the carbohydrate recognition domain. Both of these polymorphisms affect serum SFTPD levels. 6-8 However, the effects of these polymorphisms on lung function are not well documented. This study was planned to determine whether polymorphisms in SFTPD are associated with lung function in a group of healthy youngmen. Subjects and Methods The study was conducted at the Shaikh Zayed Hospital, Lahore, Pakistan, from April 2008 to August 2010, and comprised relatives and attendants of patients, as well as college and university students. The study was approved by the institutional review board. Informed consent was obtainedfromalltheparticipants.Thesubjectswereself- reportedhealthymen,anddidnotdemonstrateclinically significant signs or symptoms indicative of respiratory disease. They were not on any medications. Their lung Vol. 66, No. 9, September 2016 1137 ORIGINAL ARTICLE SNPrs3088308isariskfactorforpoorlungfunctioninhealthysmokers TaniaAhmedShakoori, 1 DonaldDonSin 2 Abstract Objective: To see if single nucleotide polymorphisms of pulmonary innate immune molecule surfactant protein D wereassociatedwithpoorlungfunctioninsmokers. Methods: ThestudywasconductedatShaikhZayedHospital,Lahore,Pakistan,fromApril2008toAugust2010,and comprised relatives and attendants of patients, as well as college and university students. Self-reported healthy smokers who demonstrated no airflow obstruction on spirometry were included. Deoxyribonucleic acid was extractedfromtheirbloodsampleandgenotypedforsinglenucleotidepolymorphismsrs721917andrs3088308by polymerase chain reaction and restriction analysis. Serum was separated for measurement of surfactant protein D levels by a commercially available enzyme-linked immunosorbent assay based kit. Lung functions were compared between subjects possessing major and minor alleles using two-tailed Student's t-test. Multiple linear regression analysis was conducted to analyse the effect of age, smoking and the two single nucleotide polymorphisms on forcedexpiratoryvolumein1second. Results: Of the 122 participants, all of whom were men, 98(80.33%) were smokers while 24(19.67%) had never smoked.Oftheformer,90(91.84%)werecurrentsmokersand8(8.16%)wereex-smokers.Theoverallmeanagewas 35.8±10.9 years. The mean surfactant protein D level was 121.4±61.6ng/ml. In case of rs3088308, all lung function variables were reduced in patients with a minor allele and the results for forced expiratory volume in 1 second (p=0.016),forcedexpiratoryvolumein1second(%)predicted(p=0.009),forcedvitalcapacity(p=0.048)andforced vital capacity (%) predicted (p=0.048) were statistically significant. Age had the highest influence on lung function (p<0.001) followed by smoking status (p=0.04) and single nucleotide polymorphisms rs3088308 minor allele (p=0.04). Conclusion: Singlenucleotidepolymorphismsrs3088308wasfoundtomodulateserumsurfactantproteinDlevels andmaybeariskfactorfordevelopmentofchronicobstructivepulmonarydiseaseamongsmokers. Keywords: Smoking,Geneticpolymorphism,SurfactantproteinD,RiskofCOPD.(JPMA66:1137;2016) 1 King Edward Medical University, Lahore, 2 University of British Columbia. Correspondence: Tania Ahmed Shakoori. Email: drtaniashakoori@kemu.edu.pk