Disease relevance of MBOAT5

• An increased prevalence of the C3 F allele has been reported in patients with partial lipodystrophy, IgA nephropathy, and Indian childhood hepatic cirrhosis [1].
• No association of the C3F allele with familial predisposition to hypertension was found [2].
• Among the treated hypertensive patients with C3F gene, 40% had coronary heart disease (CHD) compared to 6.1% among the C3F negative (P less than 0.005), and the relative risk of CHD among the treated hypertensive patients with this allele was found to be 10.2 (P less than 0.002) [2].
• C3F occurs at appreciable frequencies only in Caucasian populations and has been shown to be associated with an increased incidence of certain diseases, such as partial lipodystrophy, IgA nephropathy, and Indian childhood cirrhosis [3].
• An increased frequency of the C3F allele has been noted in a number of autoimmune and inflammatory conditions affecting the kidney, including systemic vasculitis, IgA nephropathy, and type II mesangiocapillary nephritis [4].

Psychiatry related information on MBOAT5

• The following tests were employed: simple visual reaction time (RT), critical flicker fusion frequency (C3F) and von Zerssen's self-rating scale Bf-S, assessing state of mood [5].

High impact information on MBOAT5

• The resulting restriction fragment length polymorphism (RFLP) was investigated using genomic DNA, amplified using the polymerase chain reaction; there was absolute concordance between the genomic polymorphism and the distribution of C3 S and C3 F in 50 normal subjects [1].
• C3 F, the less common variant, occurs at appreciable frequencies only in Caucasoid populations (gene frequency = 0.20) [1].
• This leads, at the translation level, to the substitution of an arginine residue (positively charged) in C3 S for a glycine residue (neutral) in C3 F [1].
• Association between coronary heart disease and the C3F-gene in essential hypertension [2].
• The dose-response curves were very similar for C3S- and C3F-coated erythrocytes [6].

Chemical compound and disease context of MBOAT5

• Alerted by our finding that myeloperoxidase has affinity for C3, and the finding of an increased frequency of the C3F allele in systemic vasculitis in a British cohort, we examined polymorphism of C3 and C4 in patients with ANCA+ small vessel vasculitis [7].

Biological context of MBOAT5

• We subsequently used oligonucleotide-primed DNA amplification to show that C3F arises from a point mutation at codon 1216 converting a deoxyadenosine for a deoxyguanosine [3].
• A North-South decreasing C3F gradient was recorded and compared to other gradients (HLA-D/DR, height, etc.) thought to be due to natural selection [8].
• Further, no associations of MHC, C3F, and immunoglobulin genes were shared by patients with RA and those with IA, indicating a different genetic basis for the two clinical entities [9].
• The average relative risk for the development of systemic vasculitis in C3F homozygotes was 5.1, indicating a gene dosage effect [10].
• The distribution of C3 phenotypes was studied in some endogamous caste groups of Andhra Pradesh, South India. The C3F allele was found to be at a low frequency and comparable to those found in castes of other regions on the Indian subcontinent [11].

Anatomical context of MBOAT5

• It has been shown that C3F differs from C3S with regard to isoelectric point as well as its ability to bind macrophages [3].
• Occurrence of the F and FS phenotype of C3 (C3F and C3FS ) was increased in the group of Crohn's disease patients (chi 2 = 2.80, p less than 0.05, one-tailed test) and in a subgroup of Crohn patients with the gastrointestinal disease process confined to ileum (chi 2 = 6.91, p less than 0.01) [12].

Associations of MBOAT5 with chemical compounds

• The result of this point mutation at the translational level is the substitution of an asparagine residue in C3S for an aspartic acid residue in C3F [3].
• The difference between human C3F and C3S results from a single amino acid change from an asparagine to an aspartate residue at position 1216 on the alpha chain of the complement component, C3 [13].
• The presence of the C3F allele was not significantly correlated with the number of rejection episodes, serum creatinine, or duration of primary nonfunction [4].

Analytical, diagnostic and therapeutic context of MBOAT5

• CR3-dependent rosette formation with the indicator erythrocytes (600 to 6000 iC3b/cell) increased from 10% to 60% in a dose-dependent manner and was closely similar for C3S and C3F [6].
• The extent of allotype conversion in C3 F/S mismatched recipients was quantified at different stages after transplantation, using an enzyme-linked immunosorbent assay specific for the HAV 4-1 polymorphism of C3 that is strongly associated with C3F [14].
• These findings suggest that C3F may be a susceptibility allele for allograft injury [4].
• Polymorphism frequencies for complement C3F (0.19) and C3S (0.81) in a sample of 137 unrelated migraineurs were found to be consistent with a control group as well as previous population studies, indicating that this common polymorphism has no association with migraine susceptibility [15].

References