No Association between Coding Polymorphism within Exon 4 of the Human Surfactant Protein B Gene and Pulmonary Function in Healthy Men

Abstract

Abstract:The coding polymorphism (rs1130866) within the surfactant protein B gene is known to associate with certain respiratory abnormalities. We investigated, using spirometry and fluorescence-based PCR, whether this variant influenced pulmonary function in healthy, nonsmoking men. We found no association of pulmonary function with genotype at the rs1130866 locus.Key words: pulmonary function, genotype.An important component of the respiratory system is the protein and phospholipid-based composition known as pulmonary surfactant. Pulmonary surfactant helps to lower the surface tension at the air-water boundary of terminal bronchioles and therefore aids alveolar gas exchange [1]. Several surfactant-associated proteins (SPs) are also known to play an active part in innate immunity by interacting with certain pathogenic organisms as well as inflammatory cells leading to cytokine production and phagocytosis [2].One of the SPs, surfactant protein B (SFPB), is encoded by a 9.5 kb gene that resides on chromosome 2 in humans [3,4]. The expression of SFPB is controlled by 5' flanking enhancer/transcription factor binding sequences [5], and transcription is sensitive to a range of modulating factors [5][6][7]. Newly translated SFPB protein undergoes complex cellular processing [8] and plays a central role in regulating surfactant composition and in the recycling of several surfactant-related molecules [1,9]. A single nucleotide polymorphism (SNP) within exon 4 of SFPB (rs1130866) is characterised by a T/C substitution. Possession of the T allele causes isoleucine to replace threonine at position 131 in the immature SFPB protein [10], resulting in the removal of an N-linked glycosylation site within the pro-SFPB peptide at the Asp 129 residue [11,12]. The polymorphism is known to associate with certain respiratory abnormalities [13,14,15], but its effect on pulmonary function as a quantifiable trait in disease-free individuals remains unclear. With this in mind, we specifically wished to assess whether the rs1130866 polymorphism could influence pulmonary function as a quantitative trait in healthy nonsmoking men.Study participants (N = 55) were all healthy, nonsmoking males aged 18-42 years. The cohort consisted of 49 Caucasians, 2 Asian, 1 Black African and 3 of the participants were of mixed ancestry. Informed consent was obtained from each individual before the start of the investigation. The study was in accordance with the Declaration of Helsinki, and the research protocol was approved by the School of Health's Research Ethics Committee. Height (m) was measured whilst standing upright, using a stadiometer, and body mass (kg) was measured using a standard balance. Body mass index (BMI) was determined by dividing body mass (kg) by height (m 2 ). Pulmonary function was assessed by the use of a handheld spirometer (Model No. 2120, Vitalograph, UK). Participants were shown how to use the device and asked to perform the manoeuvre three times with nose pinched. The mean of three manoeuvres was used for subsequent data anal...

Surfactant protein B polymorphisms, pulmonary function and COPD in 10,231 individuals

“…We, therefore, interpret this as a likely spurious finding. Our data on lung function are in accordance with a previous study on healthy males, which showed no association between rs1130866 and FEV1 % pred or FVC % pred [21].…”

“…Three functional polymorphisms in SP-B, rs1130866, rs2077079 and rs3024791, have been associated with risk and/or severity of COPD. rs1130866 abolishes an N-linked glycosylation site in SP-B, while the two (29) 5138 (50) 2130 (21) 3815 (37) 4860 (48) 1556 (15) 7724 (75) 2319 (23) 188 ( Pack-yrs of tobacco smoked were based on ever-smokers. Passive smoking was defined as affirmative responses to the questions ''Does anyone in your household smoke?''…”