Analysis of VNTRs in the Solute Carrier Family 6, Member 18 (SLC6A18) and Lack of Association with Hypertension

Abstract

We report here the distribution of VNTRs (variable number of tandem repeats; minisatellites) and polymorphic analysis of SLC6A18, which is a member of the SLC6 Na(+)- and Cl(-)-dependent neurotransmitter transporter family. In this study, DNA was obtained from 300 unrelated individuals and 205 patients with essential hypertension (EH). We then analyzed the VNTRs in the genomic DNA by searching for minisatellites of SLC6A18 using the Tandem Repeat Finder program. Eight novel VNTRs were identified: five of which were polymorphic minisatellites (SLC6A18-MS1, -MS2, -MS4, -MS5, and -MS6) and three of which were monomorphic minisatellites (SLC6A18-MS3, -MS7, and -MS8). Next, we investigated the relationship between EH and four of the polymorphic minisatellites (SLC6A18-MS1, -MS2, -MS4, and -MS6). We excluded SLC6A18-MS5 from the common/rare allele analysis, because most individuals were heterozygous and hypervariable for this locus. There were no significant differences observed in the overall distribution of these minisatellites, which indicates that these polymorphisms are not responsible for EH susceptibility in the Korean population. A segregation analysis of the minisatellites in SLC6A18 was then conducted by analyzing genomic DNA obtained from two generations of five families and from three generations of two families. The five polymorphic minisatellites were transmitted through meiosis following Mendelian inheritance, which suggests that polymorphic minisatellites could be useful markers for paternity mapping and DNA fingerprinting. In summary, we discovered five novel VNTR polymorphisms in SLC6A18; however, these variations were not associated with EH.

Susceptibility for breast cancer in young patients with short rare minisatellite alleles of BORIS

“…Recently, we demonstrated a relationship between cancer predisposition and minisatellite (VNTR, variable number of tandem repeats) variants. Rare alleles of minisatellites are associated with a high risk for various types of cancer (20)(21)(22)(23)(24). These data lend support to the concept that biologically significant consequences might result from variations in a minisatellite locus and suggests a biological basis for some cancer predisposition.…”

Variants of BORIS minisatellites and relation to prognosis of prostate cancer

“…Allelic variation at VNTRs has been related to the pathogenesis of human genetic diseases, including cancer (Krontiris et al, 1993;Bennett et al, 1995;Fiskerstrand et al, 1999;MacKenzie et al, 1999). Previously, we described an association between variation in minisatellite lengths and cancer predisposition (Leem et al, 2002;Leem et al, 2004;Jeong et al, 2007;Seol et al, 2008;Yoon et al, 2008;Lee et al, 2009;Kwon et al, 2010). In a recent study, we observed that rare alleles of BORIS-MS2 in the younger group (age, < 40 years) were associated with a statistically significant increased risk of breast cancer (Yoon et al, 2010).…”

Minisatellite 5 of SLC6A18 (SLC6A18-MS5): Relationship to Hypertension and Evolutional Level

“…이들 중 SLC6A18과 SLC6A19 는 인간의 5번 염색체 단완의 말단 5p15.33 부위에 나란히 위 치하고 있으며 [20], 이들 유전자들의 발현은 특히 전뇌와 신장 부분에서 높은 발현을 보여 [8], 여러 신경전달물질과 관련된 질병에 영향을 줄 것으로 보인다 [4,6]. [12] knockout 실험에서 고혈압이 유발됨이 보고되었다 [16].…”

“…이러한 구조적 특징을 가진 다른 유전자들에서 반복서열인 minisatellites의 길이에 따른 변이 가 질병과 연관되어 있다는 것이 밝혀졌다 [5,10,13]. SLC6A18 유전자는 염색체 말단에 존재하며, 염색체 말단 영역에 존재 하는 다른 유전자들처럼 유전자의 Intron 부위에 많은 반복서 열이 발견되었다 [9,20]. SLC6A18 유전자의 Intron 영역에서 8개의 minisatellites (VNTR, various number of tandem repeats) 영역이 밝혀졌으며, 이중 5개(SLC6A18-MS1, -MS2, -MS4, -MS5, -MS6)는 다형성을 나타내었고 나머지 3개 (SLC6A18-MS3, -MS7, -MS8)는 단형성을 나타낸다는 것이 보 고되었다 [20].…”

“…SLC6A18 유전자는 염색체 말단에 존재하며, 염색체 말단 영역에 존재 하는 다른 유전자들처럼 유전자의 Intron 부위에 많은 반복서 열이 발견되었다 [9,20]. SLC6A18 유전자의 Intron 영역에서 8개의 minisatellites (VNTR, various number of tandem repeats) 영역이 밝혀졌으며, 이중 5개(SLC6A18-MS1, -MS2, -MS4, -MS5, -MS6)는 다형성을 나타내었고 나머지 3개 (SLC6A18-MS3, -MS7, -MS8)는 단형성을 나타낸다는 것이 보 고되었다 [20]. 앞선 연구에서 SLC6A18 유전자 내의 minisatellites의 변이가 고혈압과의 관련성을 나타내는지를 조사하 기 위해, 다형성을 가진 minisatelltes 영역에서 대립형질 빈도 에 따라 1% 이상인 일반 대립형질(common alleles)과 1% 미 만인 희귀 대립형질(rare alleles)로 나누어 대조군과 고혈압 환자군을 비교하였다 [20] …”