ClinVar Genomic variation as it relates to human health

Siffert et al. (1998) described an 825C-T polymorphism in exon 10 of the gene encoding the beta-3 subunit of heterotrimeric G proteins. The T allele was associated with a splice variant in which nucleotides 498-620 of exon 9 were deleted. This in-frame deletion caused the loss of 41 amino acids and 1 WD repeat domain of the beta subunit. Increased activity of the splice variant was thought to be responsible for the previously observed enhanced signal transduction via pertussis toxin-sensitive G proteins in lymphoblasts and fibroblasts from selected patients with essential hypertension. The T allele in homozygous or heterozygous state were found in 44% of normotensive subjects and in 53.1% of hypertensive subjects. Hegele et al. (1999) found an increased body mass index among Canadian Inuits who were homozygous for the 825T allele. Siffert et al. (1999) found increased body mass index in 825T homozygotes of Caucasian, Chinese, and black-African ethnicity. Hocher et al. (2000) found an association between maternal G protein beta-3 825T allele and low birth weight in babies born to women without other risks for reduced fetal growth. Gutersohn et al. (2000) found that sedentary primiparous women homozygous for the 825T allele retained more weight after delivery, as compared with women with at least 1 825C allele. Feldman and Hegele (2000) commented on the aforementioned studies. Lindemann et al. (2001) demonstrated that the C825T allele influences cellular immune responses toward recall antigens and interleukin-2 (IL2; 147680) stimulation. Responses were increased 2- to 4-fold in homozygous 825T peripheral blood mononuclear cells compared with cells from homozygous 825C individuals. Furthermore, lymphocyte chemotaxis and CD4 (186940)-positive T-cell counts were significantly enhanced in individuals homozygous or heterozygous for the 825T allele. Lindemann et al. (2001) concluded that 825T allele status is predictive of immunocompetence and that GNB3 could be a candidate gene in disorders associated with inadequate immune response. The 825C-T polymorphism has been associated with obesity in several ethnic groups (Siffert et al., 1999), and with body mass index (BMI) the first year after pregnancy (Gutersohn et al., 2000), as well as with low birth weight (Hocher et al., 2000). Dishy et al. (2003) showed that the women homozygous for the T allele (TT) gained significantly more weight than women carrying the C allele (CC and CT groups) (P = 0.006) and had a significantly higher prepregnancy BMI (p = 0.02). (less)

Siffert et al. (1998) described an 825C-T polymorphism in exon 10 of the gene encoding the beta-3 subunit of heterotrimeric G proteins. The T allele was associated with a splice variant in which nucleotides 498-620 of exon 9 were deleted. This in-frame deletion caused the loss of 41 amino acids and 1 WD repeat domain of the beta subunit. Increased activity of the splice variant was thought to be responsible for the previously observed enhanced signal transduction via pertussis toxin-sensitive G proteins in lymphoblasts and fibroblasts from selected patients with essential hypertension. The T allele in homozygous or heterozygous state were found in 44% of normotensive subjects and in 53.1% of hypertensive subjects. Hegele et al. (1999) found an increased body mass index among Canadian Inuits who were homozygous for the 825T allele. Siffert et al. (1999) found increased body mass index in 825T homozygotes of Caucasian, Chinese, and black-African ethnicity. Hocher et al. (2000) found an association between maternal G protein beta-3 825T allele and low birth weight in babies born to women without other risks for reduced fetal growth. Gutersohn et al. (2000) found that sedentary primiparous women homozygous for the 825T allele retained more weight after delivery, as compared with women with at least 1 825C allele. Feldman and Hegele (2000) commented on the aforementioned studies. Lindemann et al. (2001) demonstrated that the C825T allele influences cellular immune responses toward recall antigens and interleukin-2 (IL2; 147680) stimulation. Responses were increased 2- to 4-fold in homozygous 825T peripheral blood mononuclear cells compared with cells from homozygous 825C individuals. Furthermore, lymphocyte chemotaxis and CD4 (186940)-positive T-cell counts were significantly enhanced in individuals homozygous or heterozygous for the 825T allele. Lindemann et al. (2001) concluded that 825T allele status is predictive of immunocompetence and that GNB3 could be a candidate gene in disorders associated with inadequate immune response. The 825C-T polymorphism has been associated with obesity in several ethnic groups (Siffert et al., 1999), and with body mass index (BMI) the first year after pregnancy (Gutersohn et al., 2000), as well as with low birth weight (Hocher et al., 2000). Dishy et al. (2003) showed that the women homozygous for the T allele (TT) gained significantly more weight than women carrying the C allele (CC and CT groups) (P = 0.006) and had a significantly higher prepregnancy BMI (p = 0.02). (less)