*3.2.2 The frequency of SNPs LRP5rs121908669 and COL1A2rs72658152*

The results of the PCR-RFLP and DNA sequencing tests for each of the two mutations were as shown in **Table 2**:

LRP5rs121908669: This study is the first of its kind in Syria as a genetic study related to LRP5, and it is the first study of its kind in the world regarding the genotyping of LRP5rs121908669.

It was found that there were 52 (34.66%) mutant cases (CC, GC) and 98 (65.33%) normal cases (GG). The mutant cases were distributed to 20 (13.3%) homozygous genotype CC and 32 (21.33%) heterozygous genotype GC.

The mutated cases (CC, GC) were distributed among low BMD cases (osteopenia, osteoporosis) and the control group (normal BMD cases) to ((19.51%) (16) (36) (52.94%)), respectively.

The proportion and number of cases of the homozygous genotype CC included 20 (13.3%). It was distributed to 5 (25%) versus 15 (75%) in the group of cases of low bone mineral density (osteopenia and osteoporosis) and the control group (cases with normal bone mineral density), respectively.

The percentage and number of cases of heterozygous genotype GC 21.33 (32%) were included. It was distributed to 11 (34.37%) compared to 21 (65.62%) in the group of BMD cases (osteopenia and osteoporosis) and the control group, respectively.

The proportion and number of cases of the normal genotype included GG 98 (65.33%). It was distributed among 66 (67.34%) compared to 32 (32.65%) in the group of carriers of low bone mineral density (osteopenia and osteoporosis) and the control group, respectively.

The CC and GC genotypes are associated with cases with normal BMD values in higher percentages than cases with low BMD values. This does not agree with the idea of an association between LRP5rs121908669 and cases with high bone mineral density—regardless of genotype—as reported in a Belgian study by Liesbeth Van Wesenbeeck et al. 2002 [17]. But it reinforces the studies indicating the existence of ethnic differences in the expression of the mutations themselves [3] (Europe, Middle East).

The association of CC and GC genotypes with low BMD cannot be neglected in some cases, contrary to the results of the Belgian study by Liesbeth Van Wesenbeeck et al. [17]. These cases may be attributed to the presence of protective factors (genetic or environmental factors) against the expression of the mutant-fixing gene (association with high BMD) or the presence of an interaction between the genes. Thus, the difference in the genetic expression of the mutation genotypes may be reflected in their effect on bone mineral density [18].


#### **Table 2.**

*Frequency of genotypes of the two studied mutations.*

## *Genetic Targets May Be a Promising Future for Osteoporosis DOI: http://dx.doi.org/10.5772/intechopen.110336*

Not all carriers of CC and GC genotypes with various BMD states show clinical symptoms of autosomal dominant osteopetrosis1 ADO1, even though it is a proven pathogenic mutation of an ADO1. This contradicts the study by Liesbeth Van Wesenbeeck et al., 2002 [17]. It has been reported that LRP5rs121908669 is associated with ADO1 which is sometimes associated with generalized bone pain and hearing loss but certainly not associated with fractures [15–17, 19]. These differences in gene expression at the BMD level may be explained by race-related factors or genetic or environmental factors affecting gene expression [15].

It is possible that the clinical features in these studied participants with bone mineral density above +1 for LRP5rs121908669 are related to HBM high bone mineral more than to ADO1, and more clinical genetic studies are needed for further understanding. High bone mineral mass (HBM) and ADOI are diseases from the osteoporosis group. The radiological features are strikingly similar but HBM patients clinically have no complaints and are completely asymptomatic [20, 21] while at least some ADOI patients present with severe pain [20, 22]. ADOI is the only type of osteopetrosis that is not associated with an increased fracture rate but HBM is associated with an increased fracture rate [17, 19, 20].

The prevalence of cases carrying GC and CC genotypes is 52 (34.66%). It is a big percentage. This contradicts studies indicating that it is a rare mutation [15].

COL1A2rs72658152: No positive result was recorded. Therefore, it was directed to study the relationship of mild OI with low bone mineral density after menopause. This conjugation has been shown to be due to the COL1A2rs72658152 mutation, according to the NCBI.
