Genetic Risk of Rheumatoid Arthritis: A Case Control Study

Abstract

Vitamin D effects are mediated by vitamin D receptors (VDRs), which are influenced by various genetic polymorphisms, including ApaI and BsmI. These polymorphisms have been linked to several diseases, including rheumatoid arthritis (RA). This study aimed to compare the frequency and association of VDR ApaI and BsmI gene polymorphisms, serum 25-hydroxy vitamin D (25-(OH)-D) levels, and calcium (Ca) levels between a RA group and a matched healthy control group. In one hundred RA patients and fifty healthy controls, the genotypes of the VDR ApaI and BsmI gene polymorphisms were analyzed using polymerase chain reaction restriction fragment length polymorphisms (PCR-RFLP). Both Serum 25-(OH)-D level and calcium level were measured in the two groups. There was no significant difference between the cases and controls regarding the VDR ApaI gene polymorphism (p = 0.89). A significant difference was observed between the cases and controls in terms of the VDR BsmI gene polymorphism (p = < 0.001). The serum levels of 25-(OH)-D and calcium were significantly lower in the RA group compared to the control group (p = 0.04 and < 0.001 respectively). Significantly higher serum vitamin D levels were associated with the aa genotype (p = 0.007). Significantly increased calcium levels were associated with the AA genotype (p = 0.02). No significant difference was found among BsmI polymorphisms regarding vitamin D and Ca levels (p = 0.25 and 0.87 respectively). Vitamin D receptor gene BsmI polymorphism but not ApaI polymorphism could be a marker of RA susceptibility. Vitamin D and Ca levels are negatively affected by RA. Vitamin D receptor gene ApaI polymorphism contributes to vitamin D and Ca levels.

Keywords: ApaI; BsmI; Calcium; Rheumatoid arthritis; Vitamin D.

Fig. 1

Mechanisms that RA can affect Ca and Vitamin D levels

Fig. 2

The main study steps

Fig. 3

Determination of genotypes for VDR– ApaI and BsmI polymorphism by using PCR-RFLP method

Fig. 4

Determination of genotypes for VDR– ApaI and BsmI polymorphism by using PCR RFLP method

Fig. 5

Comparison of serum 25hydroxy vitamin D and Ca levels category between the two groups

Fig. 6

A Comparison of serum 25hydroxy Vitamin D levels category among ApaI genotypes. B Comparison of serum Ca levels category among ApaI genotypes. Sufficient level = (≥ 30 ng/ml), insufficient level = (20 - < 30 ng/ml), and deficient level = (< 20 ng/ml)

Fig. 7

A Comparison of serum 25hydroxy vitamin D levels category among BsmI genotypes. B Comparison of serum Ca levels category among BsmI genotypes

Fig. 8

Analysis of ROC curve for 25-(OH)-D level as a predictor of hypocalcemia