Yonsei Med J.  2014 Sep;55(5):1318-1325. 10.3349/ymj.2014.55.5.1318.

Relationship of Vitamin D Binding Protein Polymorphisms and Lung Function in Korean Chronic Obstructive Pulmonary Disease

• Jung JY
• Choi DP
• Won S
• Lee Y
• Shin JH
• Kim YS
• Kim SK
• Oh YM
• Suh I
• Lee SD

• KMID: 1799497
• DOI: http://doi.org/10.3349/ymj.2014.55.5.1318

Abstract

PURPOSE
Multiple genetic factors are associated with chronic obstructive pulmonary disease (COPD). The association of gene encoding vitamin D binding protein (VDBP, GC) with COPD has been controversial. We sought to investigate the types of GC variants in the Korean population and determine the association of GC variants with COPD and lung function in the Korean population.
MATERIALS AND METHODS
The study cohort consisted of 203 COPD patients and 157 control subjects. GC variants were genotyped by the restriction fragment-length polymorphism method. Repeated measures of lung function data were analyzed using a linear mixed model including sex, age, height, and pack-years of smoking to investigate the association of GC genetic factors and lung function.
RESULTS
GC1F variant was most frequently observed in COPD (46.1%) and controls (42.0%). GC1S variant (29.0% vs. 21.4%; p=0.020) and genotype 1S-1S (8.3% vs. 3.4%; p=0.047) were more commonly detected in control than COPD. According to linear mixed model analysis including controls and COPD, subjects with genotype 1S-1S had 0.427 L higher forced expiratory volume in 1 second (FEV1) than those with other genotypes (p=0.029). However, interaction between the genotype and smoking pack-year was found to be particularly significant among subjects with genotype 1S-1S; FEV1 decreased by 0.014 L per smoking pack-year (p=0.001).
CONCLUSION
This study suggested that GC polymorphism might be associated with lung function and risk of COPD in Korean population. GC1S variant and genotype 1S-1S were more frequently observed in control than in COPD. Moreover, GC1S variant was more common in non-decliners than in rapid decliners among COPD.

Keyword

Vitamin D binding protein; polymorphism; lung function; chronic obstructive pulmonary disease

MeSH Terms

Aged
Female
Forced Expiratory Volume
Genetic Predisposition to Disease
Genotype
Humans
Male
Middle Aged
*Polymorphism, Genetic
Pulmonary Disease, Chronic Obstructive/*genetics/physiopathology
Respiratory Function Tests
Smoking
Vitamin D-Binding Protein/chemistry/*genetics
Vitamin D-Binding Protein

Figure

• 

  Fig. 1 Restriction fragment-length polymorphism analysis of GC. Eco T14 I cuts GC2 into two bands of 302 base pairs (bp) and 156 bp, whereas Hae III cuts GC1S into two bands of 295 bp and 167 bp. GC1F remains uncut by either of the enzymes (E: digested by Eco T14 I, H: digested by Hae III).

Reference

1. Snider GL. Chronic obstructive pulmonary disease: risk factors, pathophysiology and pathogenesis. Annu Rev Med. 1989; 40:411–429.

2. Behrendt CE. Mild and moderate-to-severe COPD in nonsmokers: distinct demographic profiles. Chest. 2005; 128:1239–1244.

3. Bridevaux PO, Probst-Hensch NM, Schindler C, Curjuric I, Felber Dietrich D, Braendli O, et al. Prevalence of airflow obstruction in smokers and never-smokers in Switzerland. Eur Respir J. 2010; 36:1259–1269.

4. Fletcher C, Peto R. The natural history of chronic airflow obstruction. Br Med J. 1977; 1:1645–1648.

5. Kim DS, Kim YS, Jung KS, Chang JH, Lim CM, Lee JH, et al. Prevalence of chronic obstructive pulmonary disease in Korea: a population-based spirometry survey. Am J Respir Crit Care Med. 2005; 172:842–847.

6. Lamprecht B, McBurnie MA, Vollmer WM, Gudmundsson G, Welte T, Nizankowska-Mogilnicka E, et al. COPD in never smokers: results from the population-based burden of obstructive lung disease study. Chest. 2011; 139:752–763.

7. Khoury MJ, Beaty TH, Newill CA, Bryant S, Cohen BH. Genetic-environmental interactions in chronic airways obstruction. Int J Epidemiol. 1986; 15:65–72.

8. Tager I, Tishler PV, Rosner B, Speizer FE, Litt M. Studies of the familial aggregation of chronic bronchitis and obstructive airways disease. Int J Epidemiol. 1978; 7:55–62.

9. Hersh CP, Demeo DL, Lange C, Litonjua AA, Reilly JJ, Kwiatkowski D, et al. Attempted replication of reported chronic obstructive pulmonary disease candidate gene associations. Am J Respir Cell Mol Biol. 2005; 33:71–78.

10. Hirschfeld J. Immune-electrophoretic demonstration of qualitative differences in human sera and their relation to the haptoglobins. Acta Pathol Microbiol Scand. 1959; 47:160–168.

11. Daiger SP, Schanfield MS, Cavalli-Sforza LL. Group-specific component (Gc) proteins bind vitamin D and 25-hydroxyvitamin D. Proc Natl Acad Sci U S A. 1975; 72:2076–2080.

12. Binder R, Kress A, Kan G, Herrmann K, Kirschfink M. Neutrophil priming by cytokines and vitamin D binding protein (Gc-globulin): impact on C5a-mediated chemotaxis, degranulation and respiratory burst. Mol Immunol. 1999; 36:885–892.

13. Kew RR, Sibug MA, Liuzzo JP, Webster RO. Localization and quantitation of the vitamin D binding protein (Gc-globulin) in human neutrophils. Blood. 1993; 82:274–283.

14. Piquette CA, Robinson-Hill R, Webster RO. Human monocyte chemotaxis to complement-derived chemotaxins is enhanced by Gc-globulin. J Leukoc Biol. 1994; 55:349–354.

15. Yamamoto N, Homma S. Vitamin D3 binding protein (group-specific component) is a precursor for the macrophage-activating signal factor from lysophosphatidylcholine-treated lymphocytes. Proc Natl Acad Sci U S A. 1991; 88:8539–8543.

16. Cooke NE, Willard HF, David EV, George DL. Direct regional assignment of the gene for vitamin D binding protein (Gc-globulin) to human chromosome 4q11-q13 and identification of an associated DNA polymorphism. Hum Genet. 1986; 73:225–229.

17. Cleve H, Constans J. The mutants of the vitamin-D-binding protein: more than 120 variants of the GC/DBP system. Vox Sang. 1988; 54:215–225.

18. Horne SL, Cockcroft DW, Dosman JA. Possible protective effect against chronic obstructive airways disease by the GC2 allele. Hum Hered. 1990; 40:173–176.

19. Ishii T, Keicho N, Teramoto S, Azuma A, Kudoh S, Fukuchi Y, et al. Association of Gc-globulin variation with susceptibility to COPD and diffuse panbronchiolitis. Eur Respir J. 2001; 18:753–757.

20. Ito I, Nagai S, Hoshino Y, Muro S, Hirai T, Tsukino M, et al. Risk and severity of COPD is associated with the group-specific component of serum globulin 1F allele. Chest. 2004; 125:63–70.

21. Korytina GF, Akhmadishina LZ, Ianbaeva DG, Viktorova TV. [Genotypes of vitamin-D-binding protein (DBP) in patients with chronic obstructive pulmonary disease and healthy population of Republic Bashkortostan]. Mol Biol (Mosk). 2006; 40:231–238.

22. Laufs J, Andrason H, Sigvaldason A, Halapi E, Thorsteinsson L, Jónasson K, et al. Association of vitamin D binding protein variants with chronic mucus hypersecretion in Iceland. Am J Pharmacogenomics. 2004; 4:63–68.

23. Lu M, Yang B, Cai YY. [The relationship between vitamin D binding protein gene polymorphism and chronic obstructive pulmonary disease]. Zhonghua Nei Ke Za Zhi. 2004; 43:117–120.

24. Sandford AJ, Chagani T, Weir TD, Connett JE, Anthonisen NR, Paré PD. Susceptibility genes for rapid decline of lung function in the lung health study. Am J Respir Crit Care Med. 2001; 163:469–473.

25. Schellenberg D, Paré PD, Weir TD, Spinelli JJ, Walker BA, Sandford AJ. Vitamin D binding protein variants and the risk of COPD. Am J Respir Crit Care Med. 1998; 157(3 Pt 1):957–961.

26. Bakke PS, Zhu G, Gulsvik A, Kong X, Agusti AG, Calverley PM, et al. Candidate genes for COPD in two large data sets. Eur Respir J. 2011; 37:255–263.

27. Chishimba L, Thickett DR, Stockley RA, Wood AM. The vitamin D axis in the lung: a key role for vitamin D-binding protein. Thorax. 2010; 65:456–462.

28. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis management, and prevention of chronic obstructive pulmonary disease (revised 2011). accessed on 2012 March 9. Available at: http://www.goldcopd.org/uploads/users/files/GOLD_Report_2011_Feb21.pdf.

29. Neyman J, Pearson ES. On the problem of the most efficient tests of statistical hypotheses. Philos Trans R Soc Lond A. 1933; 231:289–337.

30. Harville DA. Maximum likelihood approaches to variance component estimation and to related problems. J Am Stat Assoc. 1977; 72:320–338.

31. Kueppers F, Miller RD, Gordon H, Hepper NG, Offord K. Familial prevalence of chronic obstructive pulmonary disease in a matched pair study. Am J Med. 1977; 63:336–342.

32. Kauffmann F, Kleisbauer JP, Cambon-De-Mouzon A, Mercier P, Constans J, Blanc M, et al. Genetic markers in chronic air-flow limitation. A genetic epidemiologic study. Am Rev Respir Dis. 1983; 127:263–269.

33. Janssens W, Bouillon R, Claes B, Carremans C, Lehouck A, Buysschaert I, et al. Vitamin D deficiency is highly prevalent in COPD and correlates with variants in the vitamin D-binding gene. Thorax. 2010; 65:215–220.

34. Gomme PT, Bertolini J. Therapeutic potential of vitamin D-binding protein. Trends Biotechnol. 2004; 22:340–345.

35. Wood AM, Bassford C, Webster D, Newby P, Rajesh P, Stockley RA, et al. Vitamin D-binding protein contributes to COPD by activation of alveolar macrophages. Thorax. 2011; 66:205–210.

36. Kasuga I, Paré PD, Ruan J, Connett JE, Anthonisen NR, Sandford AJ. Lack of association of group specific component haplotypes with lung function in smokers. Thorax. 2003; 58:790–793.