Interacting contribution of the five polymorphisms in three genes of Hsp70 family to essential hypertension in Uygur ethnicity |
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Authors: | Jin-Xin Li Bao-Peng Tang Hui-Ping Sun Min Feng Zu-Heng Cheng Wen-Quan Niu |
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Institution: | (1) Cardiology Department, The First Affiliated Hospital of Xinjiang Medical University, No. 137 Liyushan Road, 830011 Urumqi, Xinjiang, China;(2) Clinical Laboratory of Diagnostic Department, The Affiliated Tumor Hospital of Xinjiang Medical University, No. 30, Beijing South Road, 830011 Urumqi, Xinjiang, China;(3) State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Ruijin Second Road 197, 200025 Shanghai, China;(4) Shanghai Key Laboratory of Vascular Biology, Shanghai Institute of Hypertension and Sino-French Research Center for Life Science and Genomics, Ruijin Hospital, Ruijin Second Road 197, 200025 Shanghai, China; |
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Abstract: | Experimental evidence suggesting that heat shock protein 70 (Hsp70) gene or associated genes are responsible for the pathophysiology
of hypertension is accumulating. In this study, we focused on five polymorphisms in three genes (HSPA1A, HSPA1B, and HSPA1L)
of Hsp70 family to explore the genetic contribution, alone and in combination, of these polymorphisms to essential hypertension
risk in a Uygur population. Genotyping was performed using PCR-RFLP and direct sequencing techniques. Data were analyzed using
haplotype and multifactor dimensionality reduction (MDR) methods. Genotype distributions of all the polymorphisms satisfied
the Hardy–Weinberg proportions in cases and controls. Statistical significance was only observed in the genotype (P = 0.0028) and (P = 0.0146) allele distributions of −110A/C polymorphism, with the −110C allele conferring a 1.45- and 2.83-fold of relative
risk, assuming the additive and recessive models, respectively, and in 1267A/G genotype distribution (P = 0.0106) with the 1267G allele conferring a 44% reduced risk. The interaction information analysis indicated that polymorphisms
−110A/C and 1267A/G had a strong synergistic effect, while polymorphisms 2074G/C and 2437T/C had a moderate synergistic effect.
Haplotype analyses further strengthened the interaction information. Using the haplotype H1 as a reference, haplotype H4 had a 40% reduced risk, while haplotypes H5 and H8 had a significantly 5.00- and 3.75-fold increased risk for essential hypertension, respectively. Taken together, our results
supported strong genetic interaction of the studied polymorphisms with the risk of having essential hypertension in Uygur
ethnicity. Functional studies are warranted to confirm or refute these findings. This is the first study to evaluate the genetic
interaction information of the Hsp70 in Uygur ethnicity, which represents one of the major nationalities in China with high
homogeneity and unique lifestyles. Moreover, we employed the haplotype and MDR methods to explore the potential interaction
of Hsp70 genetic polymorphisms in the pathogenesis of essential hypertension in Uygur. |
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Keywords: | Heat shock protein 70 Uygur Haplotype Interaction Single-locus MDR |
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