Lunqing Zhu

Association of the D repeat polymorphism in the ASPN gene with developmental dysplasia of the hip: a case-control study in Han Chinese

IntroductionDevelopmental dysplasia of the hip (DDH) is a common skeletal disease, which is characterized by abnormal seating of the femoral head in the acetabulum. Genetic factors play a considerable role in the etiology of DDH. Asporin (ASPN) is an ECM protein which can bind to TGF-β1 and sequentially inhibit TGF-β/Smad signaling. A functional aspartic acid (D) repeat polymorphism of ASPN was first described as an osteoarthritis-associated polymorphism. As TGF-β is well known as an important regulator in the development of skeletal components, ASPN may also be involved in the etiology of DDH. Our objective is to evaluate whether the D repeat polymorphism of ASPN is associated with DDH in Han Chinese.MethodsThe D repeat polymorphism was genotyped in 370 DDH patients and 445 control subjects, and the allelic association of the D repeat was examined.ResultsFrom D11 to D18, eight alleles were identified. D13 allele is the most common allele both in control and DDH groups, the frequencies are 67.3% and 58.1% respectively. In the DDH group, a significantly higher frequency of the D14 allele and significantly lower frequency of D13 was observed. The association of D14 and D13 was found in both females and males after stratification by gender. There was no significant difference in any other alleles we examined.ConclusionsOur results show an obvious association between the D repeat polymorphism of ASPN and DDH. It indicates that ASPN is an important regulator in the etiology of DDH.

Association of the leptin gene with knee osteoarthritis susceptibility in a Han Chinese population: a case-control study.

Previous studies have suggested that leptin works as a key regulator in the pathogenesis of osteoarthritis (OA), and genetic factors modulate OA. This study assessed the contribution of leptin gene (LEP) polymorphism(s) to knee OA among Han Chinese. Three tag single-nucleotide polymorphisms (SNPs) covering all those LEP SNPs of which the minor allele frequencies were over 10% were selected. Study subjects (697 patients and 699 controls) were divided into four groups (underweight, normal weight, overweight and obese) by body mass index (BMI). Allele and genotype frequencies in the three tag SNPs were significantly different in the normal weight and overweight groups. In the normal weight, overweight and obese groups, BMI (P=4.3 × 10−5, 0.012 and 0.009, respectively) and gender (P=3.5 × 10−22, 5.1 × 10−23 and 2.1 × 10−8, respectively) were effective factors. Age was an independent effective factor in the overweight group (P=0.009). Haplotypes were associated with OA in the normal weight group (CAT, P=0.015) and the overweight group (AGC, P=0.015). Our results suggest an association between LEP and knee OA in the normal weight and overweight groups among Han Chinese.

Lack of association between the CALM1 core promoter polymorphism (-16C/T) and susceptibility to knee osteoarthritis in a Chinese Han population

BackgroundCALM1 gene encodes calmodulin (CaM), an important and ubiquitous eukaryotic Ca2+-binding protein. Several studies have indicated that a deficient CaM function is likely to be involved in the pathogenesis of osteoarthritis (OA). Using a convincing genome-wide association study, a Japanese group has recently demonstrated a genetic association between the CALM1 core promoter polymorphism (-16C/T transition SNP, rs12885713) and OA susceptibility. However, the subsequent association studies failed to provide consistent results in OA patients of differently selected populations. The present study is to evaluate the association of the -16C/T polymorphism with knee OA in a Chinese Han population.MethodsA case-control association study was conducted. The polymorphism was genotyped in 183 patients who had primary symptomatic knee OA with radiographic confirmation and in 210 matched controls. Allelic and genotypic frequencies were compared between patients and control subjects.ResultsNo significant difference was detected in genotype or allele distribution between knee OA and control groups (all P > 0.05). The association was also negative even after stratification by sex. Furthermore, no association between the -16C/T SNP genotype and the clinical variables age, sex, BMI (body mass index) and K/L (Kellgren/Lawrence) score was observed in OA patients.ConclusionThe present study suggests that the CALM1 core promoter polymorphism -16C/T is not a risk factor for knee OA susceptibility in the Chinese Han population. Further studies are needed to give a global view of this polymorphism in pathogenesis of OA.