The Association of eNOS Gene Polymorphism with Avascular Necrosis of Femoral Head

Abstract

ObjectivesNecrosis of femoral head is a severe pathological state with multiple etiologies. This study investigated the association of the 27-bp repeat polymorphism in intron 4 and G894T polymorphism in exon 7 of the endothelial nitric oxide synthase (eNOS) gene with the pathogenesis of avascular necrosis of femoral head (ANFH).MethodsA total of 125 non-traumatic ANFH patients and 126 healthy controls were recruited for this study. The 27-bp repeat polymorphisms in intron 4 were analyzed by polymerase chain reaction (PCR) and sequencing. The G894T polymorphisms in exon 7 were analyzed by PCR– restriction fragment length polymorphism (PCR-RFLP) analysis.ResultsAll alleles were observed in non-traumatic ANFH patients and control subjects. Both ANFH patients and idiopathic subgroup of ANFH patients showed higher frequency of the 4a/b genotype than controls (p = 0.001 and p = 0.020, respectively). Significantly higher frequency of G/T genotype was observed in ANFH patients and idiopathic subgroup of ANFH patients compared to controls (p = 0.009 and p = 0.035, respectively).ConclusioneNOS gene polymorphisms may be a risk factor for ANFH. The 27-bp repeat polymorphism in intron 4, G894T polymorphism in exon 7, and subsequently reduced eNOS activity may be involved in the etiology of idiopathic ANFH.

Endothelial nitric oxide synthase gene polymorphism is associated with Legg-Calvé-Perthes disease

“…Since genetic background is a determinant of LCPD, extensive genomics research is required to identify polymorphic loci and elucidate the pathogenesis. eNOS gene polymorphisms have been investigated as potential risk factors in numerous vascular diseases, as aforementioned (14)(15)(16)(17)(18)(19)(20).…”

“…As a result, polymorphisms of the eNOS gene and resultant reductions in the quantity of synthesized NO are likely to lead to different types of vascular diseases, as previously mentioned; these diseases may share some common risks through inheritance or exposure. Polymorphisms of the eNOS gene have been indicated to be risk factors for avascular necrosis of the femoral head (20), an adult disease that has a similar pathogenesis to LCPD. The finding in the present study that eNOS polymorphism is associated with the pathogenesis of LCPD is, therefore, not remarkable.…”

“…The most examined and functionally associated polymorphisms are G894T in exon 7 and 27-bp variable number tandem repeat (VNTR) polymorphism in intron 4, respectively (12,13). A number of studies have observed associations between genetic polymorphisms in the eNOS gene and cardiovascular diseases, including coronary artery disease, chronic heart failure, hypertension, atherosclerosis, stroke, renal diseases and avascular necrosis of the femoral head, mainly in adult patients (14)(15)(16)(17)(18)(19)(20). Numerous studies have indicated that disruption of the blood supply to the femoral head is a key pathogenic event resulting in bone necrosis (2,21,22).…”

Endothelial Nitric Oxide Synthase Gene Polymorphism. Part 2. Polymorphic Variants T786c, 4a/B

“…Установлено, что поли-морфизм 4а/b может быть фактором риска раз-вития асептического некроза головки бедренной кости (АНГБК), в частности, в работе L. Zheng et al [33] показано, что у пациентов АНГБК наблюдалась более высокая частота генотипа 4a4b, чем в контрольной группе (р=0,001). Ана-лиз распределения частот аллелей и генотипов у лиц с остеонекрозом головки бедренной ко-сти -ОНГБК (n=68) -и здоровых лиц (n=100) показал, что частота аллеля «а» значительно выше в группе пациентов (22,8 и 9,0%, соответ-ственно, ОШ=2,98), также в контрольной группе наблюдалась более низкая частота аллеля «а» в сравнении с подгруппами с идиопатическим (16,0 и 35,6%, ОШ=2,96, р=0,0069) и вторичным ОНГБК (16 и 39,13%, ОШ=3,89, р=0,0073) [34].…”

Avascular necrosis of bone in childhood cancer patients: a possible role of genetic susceptibility

“…Polymorphisms in eNOS (endothelial nitric oxide synthase) were studied and association of the TT allele -786T/C, rs1549758 and rs1799983, 27-bp repeat in intron 4, G894T was observed (76,77,78).…”