Evaluation of Vitamin D, Vitamin D Binding Protein Gene Polymorphism with Oxidant – Antioxidant Profiles in Chronic Obstructive Pulmonary Disease Translated title: PROCENA POVEZANOSTI VITAMINA D I POLIMORFIZMA GENA ZA VITAMIN D-VEZUJUĆI PROTEIN SA OKSIDANTNIM–ANTIOKSIDANTNIM PROFILIMA U HRONIČNOJ OPSTRUKTIVNOJ BOLESTI PLUĆA

Summary

Background

The aim was to evaluate the association of plasma 25-hydroxyvitamin D (25-OHD) and vitamin D binding protein (VDBP or Gc-globin) gene polymorphism with oxidant-antioxidant profiles in patients with chronic obstructive pulmonary disease (COPD), and their role as biomarker risk factors in susceptibility and severity of COPD.

Methods

Eighty patients diagnosed with COPD (mild, moderate and severe according to lung function tests; FEV 1%) and 80 healthy controls were included in the study. Serum nitric oxide (NO) and lipid peroxide (LP), plasma reduced glutathione (RGSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) activity, 25-OHD and VDBP polymorphism were analyzed in all subjects.

Results

COPD patients had significantly decreased serum NO, plasma SOD, RGSH, GSH-Px, CAT and 25-OHD versus controls, but had significantly increased serum LP. In COPD patients, 25-OHD levels were significantly lower (41.49± 13.65 ng/mL) versus controls, but more lower in severe COPD patients (30.54±9.09 ng/mL; sensitivity 79.2%; spe - cificity 73.2%, p<0.001) versus mild and moderate COPD. VDBP genotypes frequencies were Gc1S-1S=23.8%, Gc1F-1S=28.8%, Gc1F-1F=15%, Gc1S-2=20%, Gc1F-2=11.3% and Gc2-2=1.3%. Also, VDBP variants frequencies were Gc1S=48.1%, Gc1F=35% and Gc2=16.6%. How ever, Gc1F-1S genotypes and Gc1F variants were significantly higher than in controls (10%, 12.5%; p=0.009, p=0.001, respectively). Moreover, in severe COPD patients, Gc1F-1S genotype was significantly higher than in mild COPD (41.7% vs 31.3%, p=0.04).

Conclusion

COPD patients had significantly lower plasma 25-OHD and were associated with significantly higher VDBP Gc1F-1S genotypes and Gc1F variants frequencies than controls. Low vitamin D levels and VDBP polymorphism may be important as diagnostic risk factors in the susceptibility to and severity of COPD.

Kratak sadržaj

Uvod

Cilj je bio da se utvrdi povezanost između 25-hidroksivitamina D (25-OHD) u plazmi i polimorfizma gena za vitamin D-vezujući protein ( vitamin D-binding protein, VDBP ili Gc-globin) i oksidantnih–antioksidantnih profila kod pacijenata sa hroničnom opstruktivnom bolešću pluća (HOBP), kao i njihova uloga kao faktora rizika biomarkera za podložnost i ozbiljnost HOBP.

Metode

U ovu studiju je uključeno 80 pacijenata sa dijagnozom HOBP (blag, umeren i težak oblik na osnovu testova plućne funkcije; FEV 1%) i 80 zdravih kontrolnih ispitanika. Kod svih ispitanika analizirani su nivoi azot-oksida (NO) i lipidperoksida (LP) u serumu, redukovani glutation (RGSH), superoksid-dismutaza (SOD), glutation peroksidaza (GSH/Px) u plazmi, aktivnosti katalaze (CAT), 25-OHD i polimorfizam VDBP.

Rezultati

Oboleli od HOBP imali su značajno snižene nivoe NO u serumu, SOD, RGSH, GSH-Px, CAT i 25-OHD u plazmi u poređenju s kontrolom, ali značajno povišen serumski LP. Kod obolelih od HOBP, nivoi 25-OHD bili su značajno niži (41,49±13,65 ng/mL) u odnosu na kontrolu, ali jo{ niži kod pacijenata sa teškim oblikom HOBP (30,54±9,09 ng/mL; osetljivost 79,2%; specifičnost 73,2%, p<0,001) u poređenju s blagim ili umerenim oblicima HOBP. Učestalost genotipova VDBP bila je Gc1S-1S=23,8%, Gc1F-1S=28,8%, Gc1F-1F=15%, Gc1S-2=20%, Gc1F-2=11,3% i Gc2-2=1,3%. Takođe, učestalost varijanti VDBP bila je Gc1s=48,1%, Gc1F=35% i Gc2=16,6%. Međutim, genotipovi Gc1F-1S i varijante Gc1F bili su značajno viši nego kod kontrolne grupe (10%, odnosno 12,5%; p=0,009, odnosno p=0,001). Štaviše, kod pacijenata sa teškim oblikom HOBP, genotip Gc1F-1S bio je značajno češči nego u blagoj HOBP (41,7% prema 31,3%, p=0,04).

Zaključak

Oboleli od HOBP imali su značajno niže nivoe 25-OHD u plazmi i utvr|ena je povezanost sa značajno većom učestalošću VDBP genotipova Gc1F-1S i varijanti Gc1F nego kod kontrolnih subjekata. Niski nivoi vitamina D i polimorfizam VDBP mogu biti važni kao dijagnostički faktori rizika u podložnosti i stepenu ozbiljnosti HOBP.