COMMON VARIANTS OF THE NDUFS8 GENE DO NOT CONFER GENETIC SUSCEPTIBILITY TO HYPERTENSIVE LEFT VENTRICULAR HYPERTROPHY IN HAN CHINESE

Abstract

Objective: Left ventricular hypertrophy (LVH) is the most common target organ damage in essential hypertension. The serious degree of LVH is not proportional to the history of hypertension and level of blood pressure. It is suggested that other factors than hypertension are involved in the process of cardiac remodeling in hypertensive patients. Mitochondria dysfunction plays a vital role in the pathophysiology of hypertensive cardiac hypertrophy. The NADH dehydrogenase Fe–S protein 8 (NDUFS8) is one of the highly conserved nuclear-encoded subunits existing in human mitochondrial complex I. Defects in this subunit have been associated with Leigh syndrome, which is a diverse spectrum of clinical manifestation such as hypertrophic cardiomyopathy, psychomotor impairment, difficulty feeding and respiratory abnormalities. The study aim is to investigate whether the encoding NDUFS8 gene has associated with essential hypertension and hypertensive LVH. Design and method: In total of 1604 subjects, were Chinese-Han from Yunnan province, including 985 patients with essential hypertension (470 males and 515 females) and 619 healthy controls(240 males and 379 females). Six NDUFS8 tagSNPs (rs3751084, rs999571, rs2075626, rs1104739, rs3133269 and rs11228127) were genotyped and major haplotypes consisting of these six SNPs were reconstructed for all subjects. Results: The common genetic variants of the NDUFS8 genes have not positive associated with essential hypertension and hypertensive LVH. Haplotype GGCCTA was nominally significant associated with essential hypertension (P = 0.046). Nevertheless, no significant association was detected between the haplotype and the essential hypertension after bonferrioni corrections. Intriguingly, one NDUFS8 tagSNP (rs3751084), which showed marginally significant associated with decrease serum magnesium level, the patients’ frequency of the G allele of rs3751084 was significantly higher than among the healthy controls(P = 4.69 × 10-6). Conclusions: Our study indicated that common genetic variants of the NDUFS8 gene are unlikely to be involved in essential hypertension and hypertensive LVH. Of note, we can probably consider the rs3751084 as a significant regulator to serum magnesium level. Further studies are essential to characterize the role of the rs3751084-G in Torsades de points arrhythmia with hypomagnesemia.