Premium
New susceptibility locus for obesity and dyslipidaemia on chromosome 3q22.3
Author(s) -
Dzimiri Nduna,
AlNajai Mohammed,
Muiya Paul,
Andres Editha,
Mazher Nejat,
Alshahid Maie,
Meyer Brian F
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1085.13
Subject(s) - locus (genetics) , single nucleotide polymorphism , coronary artery disease , biology , genetics , medicine , disease , gene , endocrinology , genotype
The MRAS gene resides on chromosome 3q22.3 and encodes a member of the membrane‐associated Ras small GTPase proteins, which function as signal transducers in multiple processes including cell growth and differentiation. Its role in cardiovascular disease is not fully understood yet. In a preliminary linkage study in heterozygous familial hypercholesterolaemia, we identified a locus on chr 3q, which was linked with early onset of coronary artery disease (CAD). In the present study, we investigated 7 SNPs in this region for their role as cardiovascular disease risk in 4650 Saudi individuals (2429 CAD vs 2221 angiographed controls). The rs6782181 G [1.09(1.00–1.20); p=0.048] was associated with obesity (1764 cases vs 2586 controls). The rs166195 (CT+TT)[1.14(1.00–1.29); p=0.047] was associated with low high density lipoprotein levels (1935 vs 2401). On the other hand, the rs6782181G [0.88(0.77–0.99); p=0.038] and rs253662 T [0.82(0.69–0.96); p=0.013) were protective against acquiring high low density lipoprotein‐cholesterol levels (634 vs 3696), while rs253662 TT [0.73(0.54–0.99); p=0.041) was protective against hypercholesterolaemia (1686 vs 2744). Interestingly, none of the variants showed any delineable relationship with CAD, or any of its other risk traits. These results suggest that the genomic locus for the MRAS gene confers risk for obesity and dyslipidaemia. However, since the SNPs are either intronic or reside in its 3'UTR, our findings point to the involvement of other genes or factors, rather than changes in the MRAS protein function in these events.