Journal List > J Korean Rheum Assoc > v.16(2) > 1003658

Kim and Song: Osteopontin Genetic Polymorphism and Serum Levels in Patients with Systemic Lupus Erythematosus

Abstract

Objective

A recent study suggested that a single nucleotide polymorphism (SNP) at position nt 9250 (C to T) in exon 7 of the osteopontin (OPN) gene is strongly associated with the susceptibility to systemic lupus erythematosus (SLE). This study examined the possible association between a single nucleotide polymorphism (SNP) at position nt 9250 (C to T) and SLE and measured the serum levels of OPN in Korean patients with SLE.

Methods

A total of 39 patients with SLE and 104 healthy controls were enrolled in this study. SNP located at position 9250 in the OPN gene were genotyped using the restriction fragment length polymorphism (RFLP). The serum levels of OPN in 39 patients with SLE and 20 healthy controls were determined by enzyme-linked immunosorbent assay.

Results

The allele frequencies of C and T at this position in patients with SLE were 34.6 and 65.4, whereas those in the controls were 20.7 and 79.3 (p<0.05). The serum levels of OPN in 39 patients with SLE were significantly higher than that in 20 healthy controls (49.13±26.71 versus 28.49±18.39 ng/ml, p<0.05). The increase in OPN concentration was associated with the SLE disease activity index (SLEDAI) score in all SLE patients (r=0.337, p<0.05).

Conclusion

The allele frequencies of Eta-1/osteopontin were significantly associated with SLE. Moreover, the increased serum level of OPN is associated with the SLE disease activity. However, further investigation in larger groups in Korea will be needed.

References

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Fig. 1.
Representative agarose gel electrophoresis illustrating polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) products for the Eta-1/osteopontin gene polymorphism. The nt 9250 polymorphism in exon 7: lane 1, homozygous C/C subject; lane 2, heterozygous C/T subject; lane3, homozygous T/T subject. C allele cut with Alu I generating 147- and 105-bp fragments and T allele cut with Alu I generating 61- and 44-bp fragments.
jkra-16-115f1.tif
Fig. 2.
Correlation between serum osteopontin (OPN) level and systemic lupus erythematosus disease activity index (SLEDAI).
jkra-16-115f2.tif
Table 1.
Baseline characteristics of patients with systemic lupus erythematosus
  Active SLE (n=13) Inactive SLE (n=26) p-value
Age (year) 29.92±6.59 35.81±12.16 p>0.05
Duration of disease (months) 67.31±68.60 50.96±41.54 p>0.05
Cutaneous involvement (%) 3 (23.1%) 2 (7.7%) p>0.05
Renal involvement (%) 9 (69.2%) 8 (30.8%) p<0.05
CNS involvement (%) 1 (7.7%) 0 (0.0%) p>0.05
C3 (mg/dl) 78.56±18.86 91.15±23.58 p>0.05
C4 (mg/dl) 15.04±8.95 25.84±41.49 p>0.05
C-reactive protein (mg/L) 2.60±2.63 3.48±7.19 p>0.05
ESR (mm/hr) 30.46±17.83 30.12±23.54 p>0.05
SLEDAI 12.15±3.48 3.54±2.49 p<0.05

SLE: systemic lupus erythematosus, CNS: central nervous system, ESR: erythrocyte sedimentation rate, SLEDAI: SLE disease activity index

Table 2.
Gene and allele frequencies at nt 9250 of the Eta-1/osteopontin gene in systemic lupus erythematosus patients and healthy controls
  SLE (n=39) Control (n=104) p-value
Gene frequency
Co-dominant
 T/T 18 (46.1%) 68 (65.8%) p>0.05
 C/T 15 (38.5%) 29 (27.9%) p>0.05
 C/C 6 (15.4%) 7 (6.7%) p>0.05
Dominant
 T 33 (84.6%) 97 (93.3%) p>0.05
 C 6 (15.4%) 7 (6.7%) p>0.05
Recessive
 T 18 (46.2%) 68 (65.4%) p<0.05
 C 21 (53.8%) 36 (34.6%) p<0.05
Allele frequency
 T 51 (65.4%) 165 (79.3%) p<0.05
 C 27 (34.6%) 43 (20.7%) p<0.05

SLE: systemic lupus erythematosus, nt: nucleotide

Table 3.
Difference of allele frequencies at nt 9250 of the Eta-1/osteopontin gene in SLE patients and healthy controls according to nation
Nation   Allele frequency Number p-value
USA Healthy control T (0.17)/C (0.83) 79 p<0.05
SLE patients T (0.35)/C (0.65) 81  
China Healthy control T (0.85)/C (0.15) 180 p<0.05
SLE patients T (0.74)/C (0.26) 158  
Korea Healthy control T (0.79)/C (0.21) 104 p<0.05
SLE patients T (0.65)/C (0.35) 39  

SLE: systemic lupus erythematosus, nt: nucleotide

Table 4.
Laboratory findings in systemic lupus erythematosus patients according to the gene variation at nucleotide 9250 on the Eta-1/osteopontin
Category Gene at nt 9250 on Eta-1/osteopontin Overall p-value
C/C C/T T/T
OPN (ng/ml) 66.45±43.60 41.78±22.41 49.48±21.65 NS
C3 (mg/dl) 81.47±28.98 90.11±16.05 86.63±25.67 NS
C4 (mg/dl) 51.85±86.10 17.7±6.31 16.64±8.03 NS
ESR (mm/h) 39.83±10.78 26.6±21.29 29.33±24.72 NS
hs-CRP (mg/L) 2.90±2.93 1.89±1.65 4.31±8.60 NS

OPN: osteopontin, ESR: erythrocyte sedimentation rate, hs-CRP: high sensitivity C-reactive protein, NS: not significant, nt: nucleotide

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