Predictors of decreased bone mineral density in childhood systemic lupus erythematosus: possible role of osteoprotegerin gene polymorphisms

Objectives This study aims to explore effects of osteoprotegerin (OPG) gene polymorphisms and other possible factors on bone mineral density (BMD) in children with systemic lupus erythematosus (SLE). Methods Osteoprotegerin gene rs2073617 and rs3134069 were evaluated in 74 SLE patients and 100 controls then genotypes, alleles and haplotypes’ frequencies were compared between cases and controls and between patients with BMD z-scores above and below −2 evaluated by dual energy X-ray absorptiometry (DEXA). Disease activity was evaluated by SLE disease activity index (SLEDAI). Results The patients aged 14.01 ± 2.6 years and included 57 (77%) females and 27 (36%) patients with BMD z-score below −2. Genotypes, alleles, and haplotypes frequencies did not differ between patients and controls (p>0.05 for all). Rs3134069 GG genotype and G allele (p=0.001, 0.002) and rs2073617 TT genotype and T allele (p=0.01, 0.006) were significantly higher in patients with BMD below −2. Cumulative glucocorticoids dose, disease duration, and SLEDAI scores were higher in patients with BMD below −2 (p=0.01, 0.01, <0.001, respectively). Regression analysis showed T allele of rs2073617, duration of illness (above 36 months), and cumulative SLEDAI (above 10) as independent predictors of decreased BMD (p 0.02, 0.003, and 0.002, respectively). Conclusions This is the first study to demonstrate OPG gene influence on BMD in children with SLE. The studied SNPs are not risk for developing SLE but, rs2073617 T allele is a possible predictor for reduced BMD in SLE. Other predictors include long disease duration and high activity supporting that osteoporosis in SLE is multifactorial.

Investigation of the presence of G354A (Cys87Tyr) mutation in osteoprotegerin gene in women with osteoporosis in Chaharmahal and Bakhtiari province

Background and aims: Osteoprotegerin (OPG) is a competitive inhibitor of the differentiation and activity of osteoclasts, which inhibits the final stages of osteoclast formation and induces its apoptosis. In addition, OPG is considered as one of the most important candidate genes in the pathogenesis of bone diseases such as osteoporosis and idiopathic hyperphosphatasia. The G354A (Cys87Tyr) mutation in the OPG gene leads to idiopathic hyperphosphatasia. This mutation is probably related to osteoporosis. The purpose of this study was to investigate the presence of G354A (Cys87Tyr) in women with osteoporosis in Chaharmahal and Bakhtiari province. Methods: In this descriptive-analytical study, the bone mineral density (BMD) of the femoral neck and lumbar spine of women referring to Shahrekord bone densitometry centers was measured by the X-ray absorptiometry technique in 2013-2014. Based on T-scores, people with osteoporosis were identified and 70 patients were enrolled in the study after receiving their consent. Finally, DNA was extracted from blood samples, amplified by polymerase chain reaction (PCR) technique, and sequenced by DNA sequencing method. Results: After DNA extraction from the blood, the quality and quantity were determined by gel electrophoresis and spectrophotometry, respectively. Then, the gene was amplified by the PCR method and the product was detected by gel electrophoresis, followed by sequencing the samples to investigate the presence of the mutation. Eventually, genotypes associated with Cys87Tyr mutation were not observed in the studied population. Conclusion: In the present study, the G354A (Cys87Tyr) mutation associated with idiopathic hyperphosphatasia was not found in women with osteoporosis.

Osteoprotegerin gene polymorphisms and otosclerosis: an additional genetic association study, multilocus interaction and meta-analysis

Background Otosclerosis (OTSC) is among the most common causes of a late-onset hearing loss and alteration in the osteoprotegerin (OPG) expression was suggested in the implication of OTSC pathogenesis. A case-control association study of single nucleotide polymorphisms (SNP) in the OPG gene was performed in a Tunisian-North African population composed of 183 unrelated OTSC patients and 177 healthy subjects.Results Rs3102734 and rs2073618 were significantly associated with OTSC which were predominantly detected in females after multiple corrections. The haplotypes A-A-C-G (p = 0.0.001) and A-A-C-C (p = 0.0004) were significantly associated with OTSC suggesting a reduced risk in females. Multilocus association revealed that: rs2073618 in OPG, rs39335, rs39350 and rs39374 in RELN, rs494252 in chromosome 11 and rs1800472 in TGFβ1 showed significant OTSC-associated alleles in the Tunisian samples. In addition, meta-analysis for rs2073618 SNP in Tunisian, Indian and Italian populations revealed evidence of association of the rs2073618 polymorphism with OTSC (Odds ratios of 0.826 (95% CI [0.691–0.987], p = 0.0035)).Conclusions Our findings suggest that rs3102734 and rs2073618 variants are associated with OTSC in an additional North African ethnic Tunisian population. Meta-analysis for rs2073618 based on three ethnic population revealed evidence of association with OTSC.

POLYMORPHISM OF OSTEOPROTEGERIN GENE IN INDONESIAN MEN WITH PERIODONTITIS

Objective: This work aimed to clarify the association of the severity of periodontitis and polymorphism in osteoprotegerin (OPG) (T950C) inIndonesian men.Methods: For DNA extraction, blood serum samples were used from 100 consenting Indonesian males for whom also the status of periodontitis hadbeen classified as mild, moderate, or severe. Polymerase chain reaction and restriction fragment length polymorphism techniques were applied toevaluate OPG (T950C) polymorphism, using Hind II restriction enzyme and electrophoresis on agarose gel to separate the indicative fragments.Results: The genotype distribution of the OPG (T950C) polymorphism had an appearance of an increasing percentage of TT genotype (allele T) withincreasing severitPeriodontitisy of periodontitis. The CC genotype was relatively rare (1%) in the tested Indonesian male population.Conclusions: The results show no significant association between the severity of periodontitis and polymorphism of OPG (T950C) in Indonesian men.