Kim Won-Tae, Lee Se-Ra, Roh Yun-Gil, Kim Seung Il, Choi Yung Hyun, Mun Mi-Hye, Jeong Mi-So, Koh Sang Seok, Leem Sun-Hee
1 Department of Biological Science, Dong-A University , Busan, Korea.
2 Division of Life Science Team, Korea Basic Science Institute , Daejeon, Korea.
DNA Cell Biol. 2017 Mar;36(3):227-236. doi: 10.1089/dna.2016.3448. Epub 2017 Jan 5.
The dopamine transporter SLC6A3 (DAT1) mediates uptake of dopamine into presynaptic terminals. In addition, in previous reports, hypertensive rats were associated with DAT gene, but the genetic association with SLC6A3 and hypertension is still unknown. We examined the distribution of variable number of tandem repeats (VNTRs) and conducted polymorphic analysis of the entire region of SLC6A3. Ten VNTR regions (MS1-10) were revealed throughout the intronic and UTRs; seven VNTR regions were newly isolated and three VNTRs were previously reported. Four VNTR regions (SLC6A3-MS1, -MS4, -MS8 [rs3836790], and -MS9 [rs28363170]) showed polymorphism and these loci were found to be transmitted through meiosis following Mendelian inheritance. These VNTR polymorphisms may be useful markers for paternity mapping and DNA fingerprinting. Furthermore, we also conducted a case-control study between the controls and essential hypertensive cases. Analysis of the genotypes of SLC6A3-MS8 (rs3836790) revealed that having an 8/6-repeat allele, which was only detected in hypertensive cases, was associated with hypertension (p < 0.05). Additional significant association was identified between the short 7-repeat allele of SLC6A3-MS9 (rs28363170) and the occurrence of hypertension (odds ratio 2.02; p < 0.05). These results revealed the genetic association between SLC6A3 and hypertension, and the specific VNTR alleles of SLC6A3 may be a risk factor for hypertension.
多巴胺转运体SLC6A3（DAT1）介导多巴胺摄取到突触前终末。此外，在先前的报道中，高血压大鼠与DAT基因有关，但SLC6A3与高血压的遗传关联仍不清楚。我们检查了可变数目串联重复序列（VNTRs）的分布，并对SLC6A3的整个区域进行了多态性分析。在整个内含子和非翻译区共发现10个VNTR区域（MS1 - 10）；其中7个VNTR区域是新分离的，3个VNTR区域先前已有报道。4个VNTR区域（SLC6A3 - MS1、- MS4、- MS8 [rs3836790]和 - MS9 [rs28363170]）显示出多态性，并且发现这些位点按照孟德尔遗传通过减数分裂进行传递。这些VNTR多态性可能是亲子鉴定和DNA指纹识别的有用标记。此外，我们还在对照组和原发性高血压病例之间进行了病例对照研究。对SLC6A3 - MS8（rs3836790）基因型的分析显示，仅在高血压病例中检测到的8/6重复等位基因与高血压相关（p < 0.05）。在SLC6A3 - MS9（rs28363170）的短7重复等位基因与高血压的发生之间还发现了另外的显著关联（优势比2.02；p < 0.05）。这些结果揭示了SLC6A3与高血压之间的遗传关联，并且SLC�A3的特定VNTR等位基因可能是高血压的一个危险因素。
