Elsevier

Atherosclerosis

Volume 219, Issue 2, December 2011, Pages 709-714
Atherosclerosis

Genetic variations in CYP17A1, CACNB2 and PLEKHA7 are associated with blood pressure and/or hypertension in she ethnic minority of China

https://doi.org/10.1016/j.atherosclerosis.2011.09.006Get rights and content

Abstract

Objectives

Two large-scale genome-wide association studies (GWAs) have identified multiple variants associated with blood pressure (BP) or hypertension. The present study was to investigate whether some variations were associated with BP traits and hypertension or even prehypertension in adult She ethnic minority of China.

Methods

The population of the present study comprised 4460 (1979 males and 2481 females, respectively) unrelated she ethnic minority based on a cross-sectional study from Ningde City in Fujian province of China. There were 1692 hypertensives, 1600 prehypertensives and 1168 normotensive controls, respectively. We genotyped 7 variants in CYP17A1, PLEKHA7, CACNB2, ATP2B1, TBX3-TBX5, CSK-ULK3 and SH2B3 reported by the previous GWAs on Europeans. All analyses were performed in an additive genetic model.

Results

As the minor allele of rs653178 in/near SH2B3 was very rare with the frequency of 0.018, we excluded this single nucleotide polymorphism (SNP) in the further analyses. Of the other 6 loci, linear regression analyses revealed that rs11191548 in CYP17A1 and rs11014166 in CACNB2 were significantly associated with systolic BP (β = −1.17, P = 0.002 and β = −0.50, P = 0.006, respectively), while only SNP rs11191548 was significantly associated with diastolic BP (β = −0.56, P = 0.002) after adjusted by age, sex and BMI. Two variants in CACNB2 and PLEKHA7 were found to be significantly related to hypertension (odds ratios [OR] and (95% confidence interval [CI]): 0.79 (0.65–0.97) and 1.19 (1.01–1.41), respectively) in logistic regression analyses after adjusted by age, sex and BMI. In addition, we found that combined risk alleles of the 6 SNPs increased risk of hypertension in a stepwise fashion (P for trend < 0.001). However, none of the 6 SNPs was significantly associated with BMI or prehypertension status. While logistic analysis showed that subjects with cumulative risk alleles more than 9 had significantly higher risk for prehypertension (adjusted OR: 3.10, P < 0.001) compared with those with risk alleles less than 4.

Conclusions

We replicated that variations in CYP17A1, CACNB2 and PLEKHA7 were related to BP traits and/or hypertension in She population. In addition, although we failed to observe single gene associated with prehypertension, we first found that conjoint effect of multiple risk alleles on BP might increase the risk of progressing to prehypertension.

Introduction

Hypertension is a well-known risk factor of cardiovascular disease, and becomes an important public-health challenge worldwide [1], [2]. The number of adults with hypertension in 2025 was predicted to increase by about 60% to a total of 1.56 billion (1.54–1.58 billion) [1]. It was concluded that about 13.5% of premature deaths, 54% of stroke and 47% of ischaemic heart disease worldwide were attributable to high blood pressure (BP) [2]. In addition, several surveys indicated that more than 30% of the general adult population have prehypertension, and even prehypertension were also associated with increased risk of cardiovascular disease [3], [4], [5].

Essential hypertension has a multifactorial origin arising from an interaction between susceptibility genes and environmental factors [6]. Although several lifestyle factors including sedentary lifestyle, high stress, excess salt intake, alcohol intake and lack of exercise are known to increase BP and their risk of developing hypertension [7], approximately 30–70% of BP variability in human hypertension is attributable to multiple genetic factors [8], [9], [10]. Up until now, dozens of common genetic variants associated with hypertension and BP variation have been identified in several genome-wide association studies (GWAs) [11], [12], [13], [14]. Recently, two large GWAs for BP and hypertension on about 30,000 people of European ancestry were conducted by the Global BPgen (Global Blood Pressure Genetics) and CHARGE consortium identified 13 loci associated with BP and/or hypertension [13], [14]. Considering the heterogeneity among different races and ethnic groups, it is essential to test the genetic associations with BP and hypertension previously identified for Europeans in other populations.

In multi-national China, however, each nationality has its own lifestyle and traditional hereditable background. She ethnic minority group is one of the minority nationalities in China, and approximately 25% are living in Ningde city of Fujian province. They are mainly working in the agriculture, forestry, animal husbandry, fishing, and water industry, and they have their own language and living customs different from Han population. The prevalence of hypertension was 36.09% in She population in this area [15], which was slightly higher than the prevalence of Chinese Hans with the rate of 35.84% in the same province [16]. Besides the replications were performed in Chinese Han population [17], [18] based on the GWAS results from Global BPgen and CHARGE consortium, the contributions of these loci to BP or risk of hypertension remains unknown in She population. Thus, we intended to test whether some robust association signals reported in European populations could be confirmed in She ethnic minority population.

Section snippets

Study population

A total of 4460 unrelated subjects in this analysis were taken form a cross-sectional study on She ethnic minority, aged 20–80 years, living in Ningde City of China. Subjects were excluded as following: (1) lacking data for BP and other relevant laboratory parameters; (2) with a clinical cardiovascular disease or history of secondary hypertension or kidney failure as evaluated by an extensive workup that included serum creatinine (Cr), ECG and other hematologic screening tests; (3) declined to

Results

The study subjects were composed of 1979 males and 2481 females with the mean age of 45.95 years and 47.78 years, respectively. As shown in Table 1, among 4460 subjects, 1168 were normotensives, 1600 and 1692 were prehypertensives and hypertensives, respectively. Subjects with prehypertension and hypertension had higher rate of drinkers and higher age, BMI, TC, TG, LDL-C, fasting plasma glucose, Homa-IR, creatinine and uric acid levels compared with subjects with normotension. Hypertensives had

Discussion

Although more and more BP or hypertension associated gene/loci are being identified, the replication study has played a critical role in confirming the reported BP or hypertension associated genes/loci, especially within different ethnic populations. By this replication study involving a total of 4460 Chinese She ethnic minority, we carried forward 7 SNPs which were associated with BP and/or hypertension in Global BPgen and CHARGE, and confirmed genetic associations at 3 loci with BP and/or

Acknowledgments

This work was supported by Grant C071002, 2009Y0011 for Natural Science Foundation from Fujian Province of China.

Declaration of competing interests: Nothing to declare.

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